12/5/17

Pick Your Poison: Diabetes and Psych Meds

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The American Diabetes Association said 30.3 million Americans, 9.4% of the population, had diabetes in 2015. There are 1.5 million news cases of diabetes diagnosed each year. It is the 7th leading cause of death in the U.S. with 79,535 death certificates in 2015 listing it as the underlying cause of death. A total of 252,806 death certificates listed diabetes as an underlying or contributing cause of death. If the number of deaths from diabetes were equal to 252,806, it would be the third leading cause of death in the US, according to the CDC … and psych meds increase the risk for diabetes.

SSRIs have been associated with an increased risk of diabetes, as Yoon et al. noted in “Antidepressant Use and Diabetes Mellitus.” The researchers ruled out depression itself as a potential confounding variable in the relationship between antidepressants and diabetes. Their findings suggested that antidepressant drug treatment and not the depression increased the risk of diabetes mellitus (DM). “Given the widespread use of antidepressants, the implications of the increased risk are serious.”

The authors noted that while there is disagreement as to the reason for the association between antidepressant use and DM risk, some studies “propose that antidepressants may bio-pharmacologically affect glucose homeostasis and insulin sensitivity.” In “Use of Antidepressants Linked to Diabetes,” Peter Simons of Mad in America noted a study that has supported that hypothesis. A study led by Raymond Noordam and published in The Journal of Clinical Psychiatry, found the use of SSRIs in nondiabetic participants was associated with lower insulin secretion and an increased risk of insulin dependence in type 2 diabetes in older adults.

It is biologically plausible that SSRIs decrease insulin secretion and that this might, therefore, be a mechanism underlying the previously observed association between SSRIs and increased risk of type 2 diabetes. Consequently, type 2 diabetes patients treated with SSRIs might also have a higher risk to develop insulin dependence, a condition associated with an increased risk of mortality.

The researchers also found that participants already diagnosed with diabetes who were taking antidepressants were twice as likely to start insulin treatment than those who did not take antidepressants. They said: “our data might suggest that progression of type 2 diabetes during the use of SSRIs is accelerated.” Simons commented how the higher mortality rate for individuals who require insulin treatments made this “a particularly alarming finding.”

This new study provides additional convincing evidence that although SSRIs are commonly believed to have fewer risks of adverse effects than TCAs, they still carry significant risk. This appears to be particularly relevant when it comes to patients with diabetes. Whenever antidepressant medication is considered, patients and prescribers should carefully weigh the potential risks and benefits.

There was an updated meta-analysis published in PLos One, “The Risk of New-Onset Diabetes in Antidepressant Users.” Their meta-analysis found an increased risk factor of 1.27 between exposure to antidepressants and new-onset diabetes. When they restricted the analyses to higher quality studies, the relative risk was higher. The researchers noted their findings were in line with tow previous meta-analyses that reported “a 1.5-fold increase of diabetes among AD [antidepressant] users.” In an interview with Endocrinology Advisor, the lead investigator of the study extrapolated that given a 13% prevalence rate of antidepressant use in the US, a 1.3-fold increase in diabetes risk would translate to over 1 million cases of diabetes that could be due to concurrent antidepressant use.

Pharmacy Times reported in “Atypical Antipsychotic-Induced Type 2 Diabetes” that patients with schizophrenia were at an increased risk of developing metabolic disorders like type-2 diabetes mellitus (T2DM). Schizophrenic patients had a number of risk factors for T2DM, including family history, increased body mass index (weight gain), a sedentary lifestyle and the use of atypical antipsychotics. There have been several proposed mechanisms for the association of diabetes and atypical antipsychotics, one being the weight gain associated with the medications.

A 2006 study by Alvarez-Jiménez et al. found that 78.8% of patients taking atypical antipsychotics experienced a weight gains greater than 7%, the cut off for clinically meaningful weight gain in the study. In 2004 the FDA required a warning be placed in the medication guides of all atypical antipsychotics warning of the increased risk of hyperglycemia and diabetes.

 Patients with schizophrenia are at increased risk of developing metabolic disorders like type 2 diabetes. This is due to a number of factors, including the treatment of schizophrenia with atypical antipsychotics. There are several potential mechanisms behind antipsychotic-induced diabetes, including the weight gain associated with these medications, the effects on pancreatic receptors and/or glucose transporters, or some other cause not yet discovered. Most likely, it is a combination of these effects. Of the atypical antipsychotics, clozapine [Clozaril] and olanzapine [Zyprexa] are associated with the highest incidence of metabolic dysfunction, whereas ziprasidone [Geodon] and aripiprazole [Abilify] are considered to be the least risky.

In “Antipsychotic-Induced Diabetes Mellitus” published in U.S. Pharmacist, Chhim et al. reported there are several metabolic consequences with antipsychotic use, including weight gain, hyperglycemia (abnormally high blood glucose) and dyslipidemia (an abnormal amount of triglycerides, cholesterol and/or fat phospholipids in the blood). The association of type 2 diabetes mellitus (T2DM) and antipsychotic use is supported by retrospective epidemiologic studies as well as post-marketing assessment. Data indicate the prevalence of diabetes and obesity is 1.5 to 2 times higher in people diagnosed with schizophrenia or affective disorders than the general population.

The authors noted that diabetes was reaching epidemic proportions worldwide, and the contributions of medications to the development of hyperglycemia and other metabolic problems was getting more attention.  “Pharmacists are in a unique position to counsel and encourage appropriate self-monitoring in patients receiving certain drugs, such as antipsychotics, that can contribute to the development of weight gain, hyperglycemia, and dyslipidemia.” They can encourage patients to report adverse events to other health care providers and seek therapeutic substitutions, counseling, and/or treatment for the adverse events.

Another resource addressing these concerns, one that was cited in “Antipsychotic-Induced Diabetes Mellitus,” is the “Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes.” This is a joint consensus statement from the American Diabetes Association, the American Psychiatric Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity to help reduce the risk of developing diabetes, cardiovascular disease, and other complications of diabetes.

There was a large longitudinal study done in Denmark by Rajkumar et al. that found in addition to the high risk for diabetes conferred by schizophrenia on individuals, “the risk is further increased by both first-generation and second-generation antipsychotics.” Reporting on the study for Mad in America, Bernalyn Ruiz said the authors said the prevalence of diabetes was 4 to 5 times greater in people diagnosed with schizophrenia. “After adjusting for potential confounders, the risk was elevated threefold compared to those without a schizophrenia diagnosis.” No differences were seen between first-generation and atypical antipsychotics.

This large nationwide study confirmed endogenous risk for diabetes among individuals diagnosed with schizophrenia, with risks increasing significantly when antipsychotics are prescribed.

The bottom line is that in addition to their other adverse effects, there is credible scientific evidence that antidepressants and antipsychotics increase the risk of diabetes among individuals taking them. So when you’re advised to use one of these classes of psychiatric medications, it’s a bit like being asked to pick your poison.

11/3/17

Downward Spiral of Antipsychotics

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Antipsychotic or neuroleptic drugs became big business for pharmaceutical companies about nine years ago, reaching sales of $14.6 billion in 2008. This made them the best selling therapeutic class of medications in the U.S that year. Not only are they used to treat psychosis and bipolar disorder, several have been approved as an add-on medication to treat depression. Additionally they are used off-label with children and the elderly for behavioral control. And they are the primary cause for a serious neurological disorder called tardive dyskinesia.

Tardive dyskinesia (TD) is a group of involuntary movement disorders caused by drug-induced (iatrogenic) neurological damage, primarily from antipsychotic drugs and a few others that block the function of dopamine in the brain. “TD can vary from a disfiguring grimace to a totally disabling array of spasms and often bizarre movements of any part of the body.” If TD is not identified early on and the drugs stopped, “these disorders nearly always become permanent.” Both patients and their doctors often fail to recognize or diagnose its symptoms.

The above short introduction was gleaned from Dr. Peter Breggin’s “Antipsychotic Drugs and Tardive Dyskinesia (TD) Resources Center.” If you can spare a few minutes, watch a ten-minute TD video edited by Dr. Breggin from existing videos available on the Internet. The video contains a series of individuals with the three general types of tardive dyskinesia whose ages range from pre-adolescence to seniors. These types are: tardive dystonia, a series of involuntary movements that include painful muscle contractions or spasms; tardive akathisia, psychomotor agitation; and classic tardive dyskinesia, the rapid, jerky movements or uncontrollable head bobbing or movements of the arms, hands, feet fingers or toes. The following is a reproduction of a table from Psychiatric Drug Withdrawal by Peter Breggin more fully describing the symptoms of tardive dyskinesia.

Symptoms of Tardive Dyskinesia

Tardive Dyskinesia (Classic)

Rapid, irregular (choreiform), or slow and serpentine (athetoid) movements; often bizarre looking; involving any voluntary muscle, including:

Face, eyelids and eye muscles, jaw (chewing movements, tongue biting), mouth lips, or tongue (protruding, trembling curling, cupping)

Head (nodding), neck (twisting, turning), shoulders (shrugging), back, torso (rocking movements), or abdomen

Arms and legs (may move slowly or jerk out of control)

Ankles, feet and toes; wrists, hands, and fingers (sometimes producing flexion, extension or rotation)

Breathing (diaphragm and ribs; grunting), swallowing (choking), and speaking (dysphonis)

Balance, posture, and gait (sometimes worse when slow, often spastic)

Tardive Dystonia

Often painful sustained contractions (spasms) of any voluntary muscle group; potentially causing muscular hypertrophy, arthritis, and fixed joints; frequently involving the following:

Neck (torticolis, retrocollis) and shoulders

Face (sustained grimacing and tongue protrusion)

Mouth and jaw (sustained opening or clamping shut)

Arms and hands; legs and feet (spastic flexion or extension)

Torso (twisting and thrusting movements; flexion of spine)

Eye lids (blepharospasm)

Gait (spastic; mincing)

Tardive Akathisia

Potential agonizing inner agitation or tension, usually (but not always) compelling the patient to move, commonly manifested as the following:

Restless leg movements (when awake)

Foot stamping

Marching in place, pacing

Jitteriness

Clasping hands or arms

Inability to sit still

TD can impair any muscle functions that are partially or wholly under voluntary control such as the face, eye muscles, tongue, neck, back, abdomen, extremities, diaphragm and respiration, swallowing, and vocal cords. Coordination and posture can be afflicted. TD can cause tremors, tics, and paresthesias (e.g., burning sensations, numbness). TD can also afflict the autonomic nervous system, especially impairing gastrointestinal functioning.

TD sufferers are often exhausted by these unrelenting body movements; even when they are limited to one area of the body, such as the jaw, neck or feet. They become socially withdrawn and isolated—humiliated by the stigma of their uncontrollable movement disorder. One muscle group, such as the tongue or fingers, or various muscle groups can be afflicted. TD symptoms can also change over time from one muscle group to another. This can occur over a period of minutes, days, weeks or years. “Especially in the dystonic forms, the pain can be very severe, and the physical stress can cause serious orthopedic problems.” Antipsychotic drugs are the primary cause of this neurological disorder.

Antipsychotic drugs are also called neuroleptics. Prescribers often promote them in a misleading fashion as antidepressants, mood stabilizers, bipolar drugs, sleeping pills, and behavior control drugs in children. Recent ones include Risperdal (risperidone), Abilify (aripiprazole), Geodon (ziprasidone), Invega (paliperidone), Latuda (lurasidone), Rexulti (brexpiprazole), Risperdal (risperidone), Saphris (asenapine), Seroquel (quetiapine), and Zyprexa (olanzapine). Older antipsychotics include Haldol (haloperidol) and Thorazine (chlorpromazine). [See a more complete listing of antipsychotics here]

Drug companies have made claims that the newer, so-called atypical antipsychotic drugs are less likely to cause TD, but those claims are false or misleading. A 2008 study by Chouinard found a high prevalence of DIMD (drug-induced movement disorders). Nearly 50% of patients had a definite DIMD. The authors also said that DIMD persisted with atypical antipsychotics. “It is crucial to acknowledge that there is a persistence of DIMD with atypical antipsychotics, which are not recognized and confounded with psychiatric symptoms.” Caroff, Miller and Rosenheck reported in “Extrapyramidal Side Effects” that there were no significant differences in measuring the incident rates of TD and other DIMDs between atypical antipsychotics and an older antipsychotic, perphenazine (Trilafon).

According to Dr. Breggin, TD occurs around a rate of 5 to 8 percent per year in adults up to the age of 40, with an accumulating risk of 20% to 24% after four years. The rates increase rapidly over forty. “For a 40-year-old patient, the risk is 18% at 2 years [9% per year] and 30% at 4 years.” In patients over 45, “the cumulative incident of TD after neuroleptic exposure is 26%, 52%, and 60% after 1, 2, and 3 years, respectively.”

Recently the FDA approved two medications to treat TD. Let this sink in. A serious neurological disease, which is primarily caused by a class of psychiatric medications, is being treated with another medication. Neurology Advisor interviewed two experts medical experts on the current state of treatment for TD. One of the experts interviewed said:

The main issue in the “treatment” of TD is prevention. It is important to use offending agents only when the potential benefit is higher than this risk. Once it appears, the first step is to determine whether symptoms are bothersome or disabling to warrant treatment. If possible, either discontinue the offending agent, although this might not improve symptoms permanently, and they will probably worsen initially, or change to a similar agent less likely to cause TD. In terms of prescription medications for TD, I have observed significant variability in treatment approaches depending on physician choice. Over the last few years, I personally found tetrabenazine to be the most efficient agent.

Tetrabenazine (Xenazine) was approved to treat the movement disorder associated with Huntington’s chorea, but has been used off-label to treat TD. It is now off patent and available as a generic. On patent, it sold for $152,000 per year. The generic version is $96,000 per year. However, there have been two new drugs approved specifically to treat TD: Austedo (deutetrabenazine) and Ingrezza (vabenazine). Both are being priced at around $60,000 per year. All three medications carry “black box” warnings from the FDA because of their risk for depression and suicide. You can read more about these medications here, here, here and here.

In addition to TD, antipsychotics have been linked to adverse cardio vascular events, brain shrinkage, dopamine supersensitivity, weight gain, diabetes, a shortened life span and more. The risk-benefit ratio may see a need for short-term use of antipsychotics, but the long-term benefits of their use are questioned by many credible sources. There have been follow up studies that support that concern. See this blog post by Thomas Insel, the former director of the NIMH, the National Institute of Mental Health.

It seems to be stepping onto a downward spiral to use medications with serious side effects to treat TD, a serious side effect from antipsychotics. As the above quoted expert, suggested, the best treatment for tardive dyskinesia is prevention—avoid antipsychotics if at all possible. For more information on concerns and adverse effects with antipsychotics, see: “Blind Spots with Antipsychotics” Part 1 and Part 2, “Antipsychotic Big Bang”, “Wolves in Sheep’s Clothing” and “Hollow Man Syndrome.”

10/17/17

Tell It Like It Is

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Recently I saw one of the ubiquitous “ask your doctor if … is right for you” commercials for Rexulti. The slick 90-second ad tells you that when Rexulti is added to your antidepressant, it has been shown to reduce symptoms of depression. The smiley faces used by the actors illustrate how: “Even when you’re taking an antidepressant, you may still be struggling with depression.” You learn that 2 out of 3 people taking an antidepressant may experience unresolved symptoms of depression; and that antidepressants can cause unusual changes in behavior, worsening depression and thought of suicide, especially in those 24 and younger. But you never learn that Rexulti is not an antidepressant.

The commercial never claims Rexulti is an antidepressant, but it clearly leads its viewers in that direction. Counter intuitively, in order to make the case for using Rexulti, it not-so-subtly tells you that antidepressants alone aren’t always effective, since 67% of people taking them have “unresolved symptoms” of depression. But then you learn Rexulti has been shown to reduce symptoms of depression when it is added to an antidepressant. The message is that Rexulti is effective relieving symptoms of depression. But let’s deconstruct what the commercial is telling you even further.

In the mix of the marketing rhetoric, you hear a litany of possible adverse medication side effects. The initial side effects are found with antidepressants: there could be unusual changes in behavior, worsening depression, even thoughts of suicide. “Antidepressants can increase these in those 24 and younger.” This information is legitimately about the side effects from antidepressant medications. See “Antidepressant Misuse Disorder” and “Antidepressants: Their Ineffectiveness and Risks” on this website.

Actually, Rexulti is an atypical antipsychotic or neuroleptic; in the same drug class as Abilify, Zyprexa, Seroquel and Risperdal. The other described side effects and warnings in the commercial are commonly found with atypical antipsychotics. See “Adverse Effects of Antipsychotic Medications” by Muench and Hamer for further information.

Looking further, the commercial said: “Elderly dementia patients taking Rexulti have an increased risk of death or stroke.” Antipsychotics were being used to control behavior problems in elderly patients with dementia. Then research demonstrated there was an increased risk of death in the elderly patients given antipsychotics. So the FDA issued a black box warning to that effect. There was also evidence that antidepressants increased the risk of stroke with elderly patients, thus the Rexulti warning. See “Seniors and Antipsychotics” and “Stroke Risk in Elderly Treated with Antipsychotics” for more information on this.

“Uncontrollable muscle movements” in the commercial is likely referring to tardive dyskinesia, a serious and potentially permanent neurological side effect from antipsychotics. The risks for developing metabolic syndrome (high blood pressure, high blood sugar, excess body fat at the waist, and abnormal cholesterol levels) are mentioned as well. Tardive dyskinesia and metabolic syndrome are widely acknowledged as potential adverse effects from antipsychotics, but not antidepressants. Try “Blind Spots with Antipsychotics,” Part 1 and Part 2 for a discussion on metabolic syndrome and other side effects from antipsychotics. Stiff muscles, confusion, and high fever are symptoms of “a possible life threatening condition” known as Neuroleptic Malignant Syndrome (See “Neuroleptic Malignant Syndrome”).

So you wouldn’t know Rexulti was an atypical antipsychotic or neuroleptic drug from listening to the commercial unless you knew the above were typical side effects with that class of drug. And you may not even discover this from reading the required Medication Guide, unless you knew what to look for. The FDA’s highlights of prescribing information for Rexulti, all 38 pages worth, does have a more complete discussion of the warnings and precautions as well as the adverse reactions. And Rexulti is referred to there as an atypical antipsychotic. However, in the shorter, two page medication guide, that is made available to individuals filling a prescription for Rexulti, there is no explicit reference to it being an atypical antipsychotic or neuroleptic.

The Rexulti Medication Guide does describe tardive dyskinesia, “problems with your metabolism” and Neuroleptic Malignant Syndrome as possible side effects, which are all potential side effects from antipsychotic or neuroleptic medications. But the only place in the medication guide that the word “antipsychotics” is used is in the section “What should I tell my healthcare provider before taking Rexulti?” There, the medication guide advised that if you become pregnant while taking Rexulti, you should “talk to your healthcare provider” about registering with the National Pregnancy Registry for Atypical Antipsychotics. The only place in the Rexulti medication guide the word “neuroleptic” in mentioned is when it notes how Neuroleptic Malignant Syndrome is a possible side effect.

This rhetorical sleight-of-hand is also present in the medication guides for three other antipsychotics approved by the FDA as adjunct medications for depression. Aripiprazole (Abilify), Olanzapine (Zyprexa) and Quetispine (Seroquel) all use the same descriptive technique of avoiding reference to the drugs as antipsychotics or neuroleptics in their medication guides. And several have an extended discussion of information on antidepressants. Again, someone not familiar with the medications might think they are taking an antidepressant rather than an antipsychotic medication.

The rational for this would appear to be because the initial market for antipsychotics, treating schizophrenia, is limited. Atypical antipsychotics are now the largest-selling class of drugs in the U.S. with more than $14.6 billion in annual sales for 2014. They also are the class of psychiatric drugs with the most side effects. See “Wolves in Sheep’s Clothing” and “Abilify in Denial” for more on these observations.

Another piece of information about Rexulti in contrast to the other antipsychotics approved as adjunct medications for depression is that it is the only one still on patent. Rexulti patents don’t expire until February of 2027 Abilify, Zyprexa, and Seroquel have all been approved as generics.  So Otsuka Pharmaceutical Company Ltd. has the potential for much greater profits from Resulti over the next ten years than the generic pharmaceutical companies have for the off-patent atypical antipsychotics.

There seems to be a general trend when discussing psychiatric medications to avoid any reference to them as atypical antipsychotics or neuroleptics. You can even see this in the FDA press release for the approval of Rexulti in July of 2015. This means a consumer looking for information on the potential adverse effects from an atypical antipsychotic may have some difficulty finding and then understanding what the risk is for them to take the drug.

For clarity’s sake, I think the FDA should require all consumer medication guides to clearly identify the drug class for approved psychiatric medications. They should also direct a patient to where they can find a more complete discussion of the potential adverse effects of the medication than what is contained within the brief summary of the medication guide. Confusing discussions of depression, its symptoms and the side effects from antidepressants included in antipsychotic medication guides should be clarified or removed entirely by the FDA. Additionally, there should be a truth in advertising requirement that tells it like it is for all psychiatric drug advertisements. An antipsychotic by any other name is still an antipsychotic and the commercials should say so.

07/21/17

Blind Spots with Antipsychotics, Part 2

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The American Journal of Psychiatry published an article by Goff et al. that addressed concerns that antipsychotic medications can adversely effect long-term outcomes of people with schizophrenia. Their conclusion was that there was little evidence to support “a negative long-term effect of initial or maintenance antipsychotic treatment on outcomes,” when compared to withholding medication treatment. Additionally, the researchers said while a subgroup of patients may benefit from “nonpharmacological treatment approaches,” they warned of the potential for an “incremental risk of relapse” and recommended the need for further research into the question. But did these researchers have a blind spot in how they evaluated their evidence?

In part one of this article, I reviewed some of the research evidence that supported concerns with long-term antipsychotic treatment. There was evidence supporting a link between long-term antipsychotic use and adverse cardiovascular events, brain shrinkage, and dopamine supersensitivity, as well as questions regarding the efficacy of antipsychotic maintenance treatment. There also seemed to be a disregard in Goff et al. of the evidence for the risk of metabolic syndrome with long-term antipsychotic use in their risk-benefit analysis of antipsychotic use. Yet health concerns from metabolic syndrome have been connected to the glaring difference in a shortened life expectancy, with persons suffering with serious mental illness dying 25 years earlier than the general population.

My previous encounters with Dr. Jeffrey Lieberman, who was the lead researcher for Goff et al., have led me to be cautious of his assertions without further investigation. I believe he has a serious blind spot when it comes to assessing and interpreting information counter to his position. See (“A Censored Story of Psychiatry, “Part 1, Part 2;  “Psychiatry, Diagnose Thyself!” Part 1, Part 2) for more on my concerns with Dr. Lieberman. So if there was a blind spot in Goff et al., what do other experts have to say about their conclusions?

Joanna Moncrieff wrote a response to Goff et al. on the Mad in America website, which can be accessed here. Moncrieff is a practicing psychiatrist, academic and author. She is one of the founding members and current co-chair person for the Critical Psychiatry Network, “a group of psychiatrists from around the world who are sceptical of the idea that mental disorders are simply brain diseases and of the dominance of the pharmaceutical industry.” She has written extensively on this issue, including a recent book on the troubling story of antipsychotic drugs entitled: The Bitterest Pill. You can read more about her thinking and her background on her website. She said she was shocked by how Goff et al. dismissed the concerns with long-term antipsychotic treatment and the evidence of brain impacts.

It is riddled with distortion, ignores the most pressing criticisms, and is shot through with the unexamined presumption that the multitude of problems currently labelled as schizophrenia or psychosis will one day be revealed to be due to a specific brain abnormality that is targeted by antipsychotics.

She doesn’t dispute the usefulness of antipsychotics for treating acute psychosis, what Goff et al. called initial antipsychotic treatment. Yet she noted where “decades of research into early intervention has not demonstrated that early antipsychotic treatment improves long-term outcomes.” She pointed out where Goff et al. stated the effectiveness of maintenance treatment has been well established, but then failed to acknowledge that randomised trials of maintenance treatment were typically maintenance treatment versus sudden withdrawal. “Thus they completely fail to address concerns that effects of withdrawal of long-term treatment inevitably confound such studies.”

The most worrying thing about the Goff et al. paper to Moncrieff was the minimization of the evidence that antipsychotics produce brain shrinkage. They claim that shrinkage of brain grey matter has been shown to be part of schizophrenia, claiming that brain differences were detected long before the introduction of antipsychotics. The paper they cited was a 1985 study by Bogerts and Schonfeldt-Bausch, which was a post mortem study done long after antipsychotics had been introduced.

The presence of differences between the brains of people with schizophrenia and controls does not establish that there is progression of brain volume loss, which is what has been clearly demonstrated in people and animals taking antipsychotics. There are no studies that show progressive brain changes in people diagnosed with schizophrenia or psychosis in the absence of antipsychotic treatment.

Dr. Moncrieff concluded her article by saying:

I still think antipsychotics can be useful, and that the benefits of treatment can sometimes outweigh the disadvantages, even in the long-term for some people. However, it does no one any service to pretend that they are innocuous substances that somehow magically transform (hypothetically) abnormal schizophrenic brains back to normal. Psychiatrists need to be fully aware of the detrimental effects of antipsychotics on the brain and body. They also need to acknowledge the way these drugs make life so miserable for many people, even for some who might have been even more distressed were they to be without them… Psychiatrists need to support people to evaluate the pros and cons of antipsychotic treatment for themselves and to keep doing this as they progress through different stages of their problems. To do this they need to be able to acknowledge the real nature of these drugs, and not sweep inconvenient truths under the carpet!

Miram Larsen-Barr also wrote a response to Goff et al. that appeared on Mad in America, which can be accessed here. She is a clinical psychologist with the University of Auckland, New Zealand. Larsen-Barr created and is the Service Director for Engage Aotearoa, an initiative that aims to make recovery information more easily accessible to the general public. She has “lived experience” of recovery from trauma, depression and suicidality. Her doctoral research explored experiences of taking, and attempting to stop, antipsychotic medication.

For her doctoral research she talked to 144 people who take or have taken antipsychotics. One-third thought antipsychotics had relieved their symptoms and given them back their lives—but another third said quite the opposite. She said the claim that the benefits of antipsychotic medications conclusively outweigh the adverse effects is just not true. It is true for some; entirely the opposite for others; and a mixed bag for the remaining individuals. You can access a copy of her thesis research here.

In my study, overall subjective experiences ranged on a continuum from life-saver” to hell” and every point between (Larsen-Barr, 2016). Around a third reported overall positive experiences such as A major relief from the monsters […] for me they have saved my life” and Helped me get through an unstable period of my life. And around a third of the participants reported mixed experiences such as, A short term help when needed then a burden” and A double edged sword. They help me with my bad experiences but they also take away the wind in my sails.”Another third reported wholly negative experiences such as, The worst experience of my life […] affected every aspect of my health and wellbeing. The therapeutic benefits certainly did not outweigh the costs for those who described the overall experience of taking antipsychotics as The ruin of my life or said they were Helpful to a point but […] robbed me of everything I value in myself as a person.

Larsen-Barr reported that few people in her study reported being well-informed of the potential benefits and risks before antipsychotic treatment. While about one-third reported beneficial results, 79% overall did contemplate stopping their medication, with 73% making at least one attempt. She said her study suggested the desire to stop antipsychotic medications was not just because of negative experiences. These decisions were primarily based upon whether or not taking AMs helped the person to “function in daily life.”

A full third of her survey sample had discontinued medications at the time of the study, which was similar to the stable discontinuation rate found in Harrow’s long-term study. Larsen-Barr found half of 105 survey participants who attempted to stop remained AM-free for one year or more; some over five years ago. Her research showed “withdrawal often entails a lack of information, poor support, and a range of physical, emotional, cognitive, social and functional disruptions that can be difficult to cope with, and which may include exacerbation of symptoms to the point of relapse.” For more on the Harrow study and concerns with antipsychotics, see “The Case Against Antipsychotics” by Robert Whitaker and “Worse Results with Psych Meds” on this website.

In part 1 of this article there was a discussion of how Carrie Fisher’s sudden cardiac death may have been associated with her use of psychiatric medications. Yet the possibility of her medications being a contributing factor to her death seemed to be overlooked in many articles about her unexpected death. For example, writing for Scientific American, Tori Rodriguez raised the possibility that Fisher’s bipolar disorder played a role in her death. Not the medication used to treat her bipolar disorder, but the disorder itself.

Did Carrie Fisher’s Bipolar Disorder Contribute to Her Death?” noted several possible connections to her bipolar disorder, but only made an oblique comment about how the medications may cause adverse effects like weight gain, diabetes higher triglycerides and even sudden cardiac death. Rodriguez noted how Fisher’s earlier substance abuse and struggles with her weight have been speculatively raised as contributing factors to her death. But she said one possibility that has been overlooked was the connection between bipolar disorder and cardiovascular disease and mortality. Individuals with bipolar disorder are twice as likely to develop or die from cardiovascular disease. The onset of cardiovascular disease occurs up to 17 years earlier in persons with bipolar disorder than in the general population. But as we’ve seen, that connection seems to be with the medications and not the disorder itself.

Rodriguez said Carrie Fisher “fit the bill” for several of the risk factors for sudden cardiac death at different points in her life. Then she said: ‘There is no definitive way to know whether her bipolar disorder or addiction history contributed to her death.” Yet there does seem to be a strong likelihood that not only did her use of antipsychotic medications help her be a better mother, friend and daughter, it may have contributed to her sudden cardiac death as well.

07/11/17

Blind Spots with Antipsychotics, Part 1

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Carrie Fisher was flying back to her home in Los Angeles on December 23, 2016 when she went into cardiac arrest. She was removed from the plane and later died in the hospital. Her daughter, Billie Lourd, said: ““She was loved by the world and she will be missed profoundly.” She was a well-known actress, writer and humorist. She wrote six books, some of which described her life, loves and adventures, which included drug addiction and bipolar disorder. A series of articles lamented that she was taken too soon, but there wasn’t anything said about a possible connection between her sudden cardiac death (SCD) and the medication she took for her bipolar disorder.

Fisher was a vocal mental health advocate and talked freely about her bipolar disorder and over the years. An article contained the following statements made by Fisher about her mental health and use of medication. In an interview with Diane Sawyer in December of 2000, she said: “I am mentally ill. I can say that. I am not ashamed of that. I survived that, I’m still surviving it, but bring it on. Better me than you.” At a February 2001 rally in Indianapolis for increased state funding for mental health and addiction treatment, she said: “Without medication I would not be able to function in this world. Medication has made me a good mother, a good friend, a good daughter.”

Writing for Mad in America, Corinna West raised the question of whether Fisher’s too soon passing was related to her use of psych meds. West referred to an article in the European Heart Journal by Honkola et al. that concluded: “The use of psychotropic drugs, especially combined use of antipsychotic and antidepressant drugs, is strongly associated with an increased risk of SCD at the time of an acute coronary event.” Variety reported Carrie Fisher was taking Prozac (an antidepressant), Abilify (an antipsychotic) and Lamictal (a mood stabilizer).

This study confirms that combining antidepressants and old school [first generation] antipsychotics causes an 18-fold increase in death during a cardiac event. Combining antidepressants with any antipsychotic causes an over 5-fold increase in relative risk of death during a cardiac incident.

To put this into some context, West noted: “Vioxx was pulled from the market for a 2-fold increase in relative risk factor of strokes and heart attacks.” It may have led to the death of 50,000 to 70,000 people while it was on the market. She then did some speculative calculations and suggested psych meds may contribute to 74,191 additional heart attacks annually and 33,386 deaths from SCD per year.

She also noted how people with serious mental illness have a 25-year lower life expectancy than others and a significantly greater risk of myocardial infarction. The NASMHPD “Morbidity and Mortality Report” said that it has been known for several years that people with serious mental illness die younger than the general population. “In fact, persons with serous mental illness (SMI) are now dying 25 years earlier than the general population.” The report also said people with SMI also suffer from a greater percentage of modifiable risk factors associated with cardiovascular disease, such as obesity, smoking, diabetes, hypertension and dyslipidema (high cholesterol). Corrine West noted the data from the “Morbidity and Mortality Report” showed that psychiatric drugs increased 4 of the top 5 normal risk factors for cardiac disease. Smoking was included as a risk factor because many individuals using psych meds find the nicotine helps relieve some of the numbness caused by the meds. See the following chart from the report.

There is increasing evidence of multiple adverse effects from the long-term use of antipsychotics in addition to the risk of SCD. Murray et al. concluded there was a lack of evidence for the long-term effectiveness of prophylactic (maintenance) antipsychotic use; and a growing concern with the cumulative effects of antipsychotics on physical health and brain structure. “There is enough evidence concerning the adverse effects of antipsychotics on physical health to compel psychiatrists to act.”

Murray et al. said long-tem maintenance treatment with antipsychotics was “based on hope rather than evidence.” They pointed to two serious methodological problems. First, studies claiming that antipsychotic maintenance treatment substantially reduced the risk of relapse were often limited to two years of follow-up. Second, the studies compared schizophrenic patients continuing on antipsychotics with those who stopped taking antipsychotics, not individuals who never used the drugs. So the withdrawal effect from antipsychotics in the discontinuation group influenced the higher relapse rates, making it a confounding variable to the supposed positive results with antipsychotic maintenance treatment.

The Murray et al. researchers did think there was no clear link between antipsychotic-associated changes in brain structure and cognitive decline or functional impairment. However, studies like that of Ho et al. suggested antipsychotics can “have a subtle but measurable influence on brain tissue loss over time.” Ho et al. said there was also a problem with dopamine receptor supersensitivity in some antipsychotic users. This supersensitivity could be a factor in the decreased efficacy of antipsychotics with continued prescription; and it may contribute to relapse when an individuals stops using antipsychotics. “There is an urgent need for neurochemical imaging studies addressing the question of dopamine supersensitivity in patients.”  In their conclusion, the researchers gave the following recommendations.

[The wise psychiatrist] will treat acute psychosis with the minimum necessary dose of antipsychotics, employing weight sparing antipsychotics wherever possible; dopamine partial agonists have this property and may also be less likely to induce dopamine supersensitivity. Following recovery, the psychiatrist should work with each patient to decrease the dose to the lowest level compatible with freedom from troublesome psychotic symptoms; in a minority of patients, this level will be zero.

You can read a summary review of the study by Justin Karter on Mad in America here.

Not all of the above-cited researchers agreed with the conclusions of each other. But collectively they pointed to evidence of a link between antipsychotics and adverse cardio vascular events, brain shrinkage, and dopamine supersensitivity.  Murray et al. also suggested that studies of long-tem antipsychotic maintenance treatment unfairly stacked their results in favor of antipsychotic maintenance by using patients who were withdrawn/discontinued from using antipsychotics as their control group. So when the recent press release from Columbia Medical Center regarding Goff et al. concluded the benefits of antipsychotics outweigh the risks was disconcerting and confusing at first. The Goff et al. abstract asserted: “Little evidence was found to support a negative long-term effect of initial or maintenance antipsychotic treatment on outcomes, compared with withholding treatment.”

The press release acknowledged the above concerns that antipsychotic medications have been said to have toxic effects and negatively impact long-term outcomes. However it went on to say that if this view was not justified by data, it had the potential to “mislead some patients (and their families) to refuse or discontinue antipsychotic treatment.” Therefore a team of researchers led by Jeffrey Lieberman, the Lawrence C. Kolb Professor and Chairman of Psychiatry at Columbia University College of Physicians and Surgeon, undertook “a comprehensive examination of clinical and basic research studies that examined the effects of antipsychotic drug treatment on the clinical outcomes of patients and changes in brain structure.” Lieberman was liberally quoted in the Columbia press release with regard to their findings supporting how the benefits of antipsychotics outweigh the risks. He said:

The evidence from randomized clinical trials and neuroimaging studies overwhelmingly suggests that the majority of patients with schizophrenia benefit from antipsychotic treatment, both in the initial presentation of the disease and for longer-term maintenance to prevent relapse. . . . Anyone who doubts this conclusion should talk with people whose symptoms have been relieved by treatment and literally given back their lives.

Lieberman went on to suggest that only a very small number of individuals recover from an initial psychotic episode without the use of antipsychotic maintenance treatment. “Consequentially, withholding treatment could be detrimental for most patients with schizophrenia.” He acknowledged where rodent studies suggested antipsychotics can sensitize dopamine receptors, but “there is no evidence that antipsychotic treatment increases the risk of relapse.” Further, although antipsychotic medications can increase the risk of metabolic syndrome, which is linked to heart disease, diabetes and stroke, their study did not include a risk benefit analysis of this concern.

Wait a minute. Why didn’t their study include a risk benefit analysis for metabolic syndrome? It seems to be one of the most reliably documented adverse effects, as noted above. Could it be that the intended message of the research—namely how strong evidence supports the benefits of antipsychotic medications—would not have been as clearly communicated if the risk benefit analysis concluded there was a substantial risk of metabolic syndrome? By the way, according to the Mayo Clinic,

Metabolic syndrome is a cluster of conditions — increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels — that occur together, increasing your risk of heart disease, stroke and diabetes. Having just one of these conditions doesn’t mean you have metabolic syndrome. However, any of these conditions increase your risk of serious disease. Having more than one of these might increase your risk even more. If you have metabolic syndrome or any of its components, aggressive lifestyle changes can delay or even prevent the development of serious health problems.

Dr. Lieberman has been a vocal advocate of modern psychiatry and equally critical of those who question many of its claims, as with those documented here. My previous encounters with his presentation of evidence and data, like his discussion of the conclusions of Goff et al. above, have led me to be skeptical of his conclusions without further investigation. I believe his fervent desire to defend modern psychiatry and current psychiatric methods has distorted how he interprets and presents conflicting evidence. He seems to have a blind spot when assessing and interpreting evidence counter to his position. The above question about the failure to include a risk benefit analysis of metabolic syndrome is one illustration of what I mean.

So what do others have to say with regard to the Goff et al. study? We’ll look at some of those critiques in part 2 of this article.

06/9/17

Worse Results with Psych Meds

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Psych meds are popular. One in six U.S. adults (16.7% of 242 million) reported filing at least one prescription for a psychiatric medication in 2013. That increased with adults between the ages of 60 and 85, where one in four (25.1%) reported using psych meds. Only 9% of adults between the ages of 18 and 39 reported using one or more psych drugs. Most psychiatric drug use was long-term, meaning patients reported taking these meds for two years or more; 82.9% reported filling 3 or more prescriptions in 2013. “Moreover, use may have been underestimated because prescriptions were self-reported, and our estimates of long-term use were limited to a single year.”

The above findings were reported in a research letter written by Thomas Moore and Donald Mattison in JAMA Internal Medicine. Their findings got a fair amount of media attention, including articles in Live Science (here), The New York Times (here), Mad in America (here), Psychology Today (here) and even Medscape (here).

Moore said the biggest surprise was that 84.3% of all adults using psychiatric medication (34.1 million) reported using these meds long-term, meaning over two years. He said the high rates of long-term use of psych meds raises the need for closer monitoring and a greater awareness of the potential risks.

Both patients and physicians need to periodically reevaluate the continued need for psychiatric drugs. . . This is a safety concern, because 8 of the 10 most widely used drugs have warnings about withdrawal/rebound symptoms, are DEA Schedule IV, or both.

The ten most commonly used psychiatric drugs in ranked order were:

  1. Sertraline (Zoloft, an SSRI antidepressant)
  2. Citalopram (Celexa, an SSRI antidepressant)
  3. Alprazolam (Xanax, a benzodiazepine for anxiety)
  4. Zolpidem tartrate (Ambien, a hypnotic prescribed for sleep)
  5. Fluoxetine (Prozac, an SSRI antidepressant)
  6. Trazodone (an antidepressant often prescribed for sleep)
  7. Clonazepam (Klonopin, a benzodiazepine for anxiety)
  8. Lorazepam (Ativan, a benzodiazepine for anxiety)
  9. Escitalopram (Lexapro, an SSRI antidepressant)
  10. Duloxetine (Cymbalta, an SNRI antidepressant)

Drawing on data from a different source in “Drugs on the Mind” for Psychology Today, Hara Estroff Marano said the Institute for Healthcare Informatics (IMS) reported there were 4.4 billion prescriptions dispensed in 2015, with total spending on medicines reaching $310 billion. “Over a million of the prescriptions written for a psychiatric drug were to children 5 years of age or younger.” There were 78.7 million people in the U.S. using psychiatric meds. Within this group, 41.2 million were prescribed one or more antidepressants; 36.6 million were given anti-anxiety medications; and 6.8 million were given antipsychotics.

These figures were different than the percentages reported above from the Moore and Mattison study. Moore and Mattison found that 12% (29 million) reported using antidepressants; 8.3% (20 million) reported using anxiolytics and 1.6% (3.9 million) reported using antipsychotics. Their 1 in 6 (16.7%) figure would then be 40.4 million people using at least one psychiatric medication. Regardless of which data source you use, there are millions of U.S. citizens taking at least one psychiatric drug and therefore at risk of experiencing the adverse effects associated with these drug classes.

Anatomy of an Epidemic by Robert Whitaker described how psychiatric drugs seem to be contributing to the rise of disabling mental illness rather than treating those who suffer from it. What follows is a sampling of comments from Anatomy that he made about benzodiazepines (anxiolytics), which are widely used to treat anxiety and insomnia. Whitaker said long-term benzodiazepine use can worsen the very symptoms they are supposed to treat. He cited a French study where 75 percent of long-term benzodiazepine users  “. . . had significant symptomatology, in particular major depressive episodes and generalized anxiety disorder, often with marked severity and disability.”

In addition to causing emotional distress, long-term benzodiazepines usage also leads to cognitive impairment (137). Although it was thirty years ago that governmental review panels in the United States and the United Kingdom concluded that the benzodiazepines shouldn’t be prescribed long-term … the prescribing of benzodiazepines for continual use goes on (147).

In her article for Medscape, Nancy Melville pointed out the CDC found zolpidem (a so-called “Z” drug) was the number one psychiatric linked to emergency department visits. As many as 68% of patients used it long-term, while the drug is only recommended for short-term use. Up to 22% of zolpidem users were also sustained users of opioids.

Among the concerns with antidepressants are that they are not more effective than placebos (see discussions of the research of Irving Kirsch, starting here: “Do No Harm with Antidepressants”). In some cases they contribute to suicidality and violence (see “Psych Drugs and Violence” and “Iatrogenic Gun Violence”) and they have a risk of withdrawal symptoms upon discontinuation.

In a systematic review of the literature, Fava et al. concluded that withdrawal symptoms might occur with any SSRI. The duration of treatment could be as short as 2 months. The prevalence of withdrawal was varied; and there was a wide range of symptoms, encompassing both physical and psychological symptoms. The table below, taken from the Fava et al. article, noted various signs and symptoms of SSRI withdrawal.

The withdrawal syndrome will typically appears within a few days of drug discontinuation and last for a few weeks. Yet persistence disturbances as long as a year after discontinuation have been reported. “Such disturbances appear to be quite common on patients’ websites but await adequate exploration in clinical studies.”

Clinicians are familiar with the withdrawal phenomena that may occur from alcohol, benzodiazepines, barbiturates, opioids, and stimulants. The results of this review indicate that they need to add SSRI to the list of drugs potentially inducing withdrawal phenomena. The term ‘discontinuation syndrome’ minimizes the vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome’.

Updating his critique of the long-term use of antipsychotics in Anatomy of an Epidemic, Robert Whitaker made his finding available in a paper, “The Case Against Antipsychotics.” There are links to both a slide presentation and a video presentation of the information included in his paper. The breadth of material covered was difficult to summarize or select out some of the more important findings. Instead, we will look at what Whitaker said was the best long-term prospective study of schizophrenia and other psychotic disorders done in the U.S. The Harrow study assessed how well an original group of 200 patients were doing at various time intervals from 2 years up until 20 years after their initial hospitalization for schizophrenia. In his paper, Whitaker reviewed the outcome for these patients after 15 and 20 years of follow up.

Harrow discovered that patients not taking medication regularly recovered from their psychotic symptoms over time. Once this occured, “they had very low relapse rates.” Concurrently, patients who remained on medication, regularly remained psychotic—even those who did recover relapsed often. “Harrow’s results provide a clear picture of how antipsychotics worsen psychotic symptoms over the long term.” Medicated patients did worse on every domain that was measured. They were more likely to be anxious; they had worse cognitive functioning; they were less likely to be working; and they had worse global outcomes.

There is one other comparison that can be made. Throughout the study, there were, in essence, four major groups in Harrow’s study: schizophrenia on and off meds, and those with milder psychotic disorders on and off meds. Here is how their outcomes stacked up:

As Whitaker himself noted, his findings have been criticized from several individuals. However, he answered those critiques and demonstrated how they don’t really hold up. Read his paper for more information. But his conclusions about the use of antipsychotic medications are not unique. In the article abstract, for “Should Psychiatrists be More Cautious About the Long-Term Prophylactic Use of Antipsychotics?” Murray et al. said:

Patients who recover from an acute episode of psychosis are frequently prescribed prophylactic antipsychotics for many years, especially if they are diagnosed as having schizophrenia. However, there is a dearth of evidence concerning the long-term effectiveness of this practice, and growing concern over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss of effectiveness through the development of supersensitivity of the dopamine D2 receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should be able to achieve a good outcome in the long term either with no antipsychotic medication or with a very low dose.

All three classes of psychiatric medications reviewed here have serious adverse effects that occur with long-term use. In many cases, they lead to a worsening of the very symptoms they were supposed to “treat.” Increasingly, it is being shown that the psychiatric drug treatments are often worse than the “mental illness” they allegedly treat.

03/17/17

Broken Promises with Abilify

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Based upon sales data for the world’s 15 top selling drugs, Abilify was ranked fourth, with $9.3 billion of sales in 2014. Reflect for a moment what this means; an antipsychotic drug had greater worldwide sales than Nexium (for acid reflux) and Crestor (for high cholesterol). While it is an approved medication in the US for bipolar 1 and schizophrenia, it is likely these sales figures reflect it use as an adjunct medication for major depression. Oh, and along with other antipsychotics, it is used off label to treat several other behavioral disorders such as Tourette’s and irritability associated with autism. This popularity is despite the reality that antipsychotics have a high incidence of negative side effects—greater than antidepressants and anti-anxiety medications.

The problems with antipsychotics have been known for a few years. As far back as 2010, Robert Field wrote: “Antipsychotic Medications Are Spelling Legal Trouble for Drugmakers” for the journal Pharmacy and Therapeutics. In 2007, Bristol-Myers Squibb paid $515 million to settle charges of illegally marketing Abilify for children and the elderly, “In contravention of FDA-approved labeling.” But that hasn’t been the end of legal troubles regarding Abilify. On May 3, 2016, the FDA published a safety announcement warning that Abilify (aripiprazole) can trigger impulse-control problems such as “compulsive or uncontrollable urges to gamble, binge eat, shop, and have sex.” These urges reportedly stop when the drug is discontinued or the dose reduced.

These compulsive behaviors can affect anyone who is taking the medicine. As a result, we are adding new warnings about all of these compulsive behaviors to the drug labels and the patient Medication Guides for all aripiprazole products.

The mechanism of action for Abilify is not clearly understood, but researchers think it over-stimulates dopamine 3 (D3) reward receptors, which are mainly located in the limbic system. This in turn triggers the compulsive behaviors. Gaboriau et al. reviewed case reports in Addictive Behaviors and indicated that pathological gambling (PG) appeared as quickly as a few days after Abilify was started; sometimes after an increase in dosage with 7 of the 8 case reports. PG then decreased after Abilify treatment was stopped or decreased; again sometimes as soon as a few days afterwards.

Limitations on the Gaboriau et al. findings included that most of the patients were already gambling before starting with Abilify. Several patients also had a history of substance use disorders. However, the authors noted that the same D3 receptor was implicated in another study by J. E. Ahiskog of the dopamine agonist medications, pramipexole and ropinirole, which are commonly used to treat Parkinson’s disease.

This hyperstimulation would apparently be particularly enhanced in cases of a previous treatment by antipsychotics acting as a dopaminergic receptors antagonist, owing to the up-regulation and the dopaminergic receptor hypersensitivity processes. The partial agonist action of aripiprazole then causes stronger effects. Moreover, the intrinsic dopamine pharmacodynamic activity of aripiprazole imparts it less action agonist than a complete agonist, which could explain why the occurrence of PG is sometimes late or due to dosage increase.

The above concern with Abilify was also supported by the findings of a study by Moore, Glenmullen and Mattison reported in JAMA Internal Medicine. Adverse drug event reports received by the FDA from 2003 to 2012 were reviewed for the six dopamine receptor agonist drugs marketed in the U.S. The review identified 1580 reports of impulse control disorder events, including pathological gambling, hypersexuality, compulsive shopping and others. They also detected weaker signals for antidepressants and antipsychotics.

The Daily Beast reported on a massive tort lawsuit being filed against Otuska and Bristol-Myers Squibb charging that Abilify created a compulsion for sex and gambling. Moreover, the suit claims the drug makers knew of the serious side effects because of required changes in Canadian and European warning labels, but waited for years to warn U.S. consumers. Thomas Moore of the Institute for Safe Medication Practices explained the drug triggers an urge to gamble constantly, sometimes with people with no prior interest. “It might be people starting to spend $300 a week on lottery tickets, and in other cases people will gamble away tens of thousands of dollars.” Moore went on to say:

We live in a society whose rules and laws assume people are responsible for their actions, including running up a large gambling debt. . . But we have scientific evidence that sometimes a drug can trigger a pathological urge to gamble so severe it can ruin someone’s life.

A woman who began using Abilify to aid in treating her PTSD developed a compulsive gambling problem. She used up her unemployment checks, pawned her husband’s automotive tools, and lied about needing money for baby formula. “Nothing was off-limits when it came to getting the money I needed to keep up the ruse.” She’d stuff her bed at night in order to fool her husband into thinking she was asleep when she was actually at the casino playing the slot machines.

Another woman developed hypersexuality. She started with online chatting with men. She became obsessed with sexual fantasies and took sexualized pictures of herself and sent them to select ‘friends.’ “I just couldn’t stop with the pictures and fantasies.” She also went on shopping sprees. Then her husband caught her. “The drug has destroyed my life, my reputation, and the lives of those I love.”

The website RxISK has multiple reports on adverse events with Abilify. “Abilify from the Inside Out” described bouts of akathisia (a state of agitation, distress, and restlessness), unusual aggression or anger, first time episodes of psychosis, suicidality, at least three confirmed suicides, movement disorders such as tremors, and (of course) compulsive gambling. The author said the reports were hard for him to read. Since most of the patients were on several meds, some patients couldn’t be sure that Abilify alone caused the problem. Even stopping Abilify was related to adverse drug events.

The above noted 2007 lawsuit, where Bristol-Myers Squibb paid $525 million to settle charges of illegal marketing, unveiled some of the marketing records for Abilify. Remember, one of the concerns was that it was illegally marketed for use with the elderly. The sales reps for Abilify would invite nursing home staff to picture a new resident, hunched in their chair, staring off into space because of ‘depression.’ “’Who wants to see that when they come to visit Mom on a Saturday?’ the reps would ask. ‘Wouldn’t we like to see her up and about, looking lively?’” The sale pitch worked. One woman wrote the following to RxISK:

I have seen many commercials about how drugs like Abilify can perk people right up. . . So I was not only disappointed and frightened by the results, but felt once again tricked and exploited by the big promises that drug companies make but never seem to keep.

I wish the above concerns weren’t true. But I’ve known individuals whose experiences on Abilify are consistent with the above discussion of its adverse effects. Sadly, even when sanctions are in the millions of dollars, the profits are higher. And it seems the cards are stacked against pharmaceutical companies being held accountable financially. So consumers have to fight against this by refusing to use Abilify and telling others what you have read here. If you are interested in other articles on the problems with Abilify and the other antipsychotics, try: “Antipsychotic Big Bang” or “Abilify in Denial” on this website.

03/8/16

Chemical Straightjackets for Children

© Sangoiri | Dreamstime.com

© Sangoiri | Dreamstime.com

In a five-minute video, “Stop the Psych Drugging of Children—Now!, Dr. Peter Breggin made some alarming statements about the consequences of several decades of giving children psychiatric drugs. He said we have parents who believe their children are incorrigible. And we have children who grow up thinking they are defective and need psychiatric drugs. Many of the children who started out with a mere ADHD diagnosis when they were younger are growing up to be “career mental patients, taking multiple psychiatric drugs.” In an article he published in the journal Children & Society, Breggin reviewed in more detail many of the concerns he just touched on in his video. Here, I want to look at the growing problem of using antipsychotics with children.

Mad in America reported that a study published in JAMA Psychiatry indicated that the majority of children, adolescents and young adults who are prescribed antipsychotic medications have not been diagnosed with a mental disorder. “Most of the younger children (60.0%), older children (56.7%), adolescents (62.0%), and young adults (67.1%) treated with antipsychotics had no outpatient or inpatient claim that included a mental disorder diagnosis.” Among the children who do have a diagnosis for a mental disorder, many of them are being prescribed antipsychotics off label.

In other words, while antipsychotics are only approved to treat children diagnosed with schizophrenia and bipolar disorder, children with diagnoses like ADHD are being given these powerful drugs to “treat” their behavior problems. In addition, very few of the children receiving antipsychotics also receive psychotherapeutic care. Mark Olfson, the lead author of the study said:

Relatively few of these young people are receiving psychotherapy. We may need to put greater effort into increasing access to psychosocial interventions that can treat symptoms and behaviors that are currently being addressed with antipsychotic medications.

In the same issue of JAMA Psychiatry in which the Olfson et al. article was published, Drs. Carroll and Blader acknowledged in “Antipsychotic Use in Youth Without Psychosis” that the use of antipsychotic medications has been increasing since the mid-1990s. They added this pattern was most pronounced in the U.S. They affirmed evidence suggests that second-generation antipsychotic use was chiefly with children with aggression and behavioral problems, ADHD, and disruptive behavior disorders. “Although antipsychotics are clearly effective for aggressive behaviors … other interventions with lower adverse effect burdens, when implemented adequately, can avert the need for antipsychotic treatment.”

Reporting for the StarTribune, Gail Rosenblum noted that in 2014 20,000 prescriptions for antipsychotic medications were written for children 2 and younger. According to IMS Health, a healthcare data company, that was a 50% increase over the year before. Turn to the article to see a photo of a child playing with Lego-like blocks branded with “Risperdal” at a pediatrician’s office.

IMS found that at least 10,000 children, ages 2 and 3, were prescribed medications such as Adderall to treat attention deficit hyperactivity disorder (ADHD). The protocol falls outside of American Academy of Pediatrics guidelines. Children younger than age 2 received prescriptions for risperidone (commonly known as Risperdal), quetiapine (Seroquel) and the antidepressant Prozac.

In his Children & Society article, Dr. Breggin noted where the so-called second-generation antipsychotics cause the same adverse effects as the older antipsychotics. These adverse effects include: “lobotomy-like indifference and apathy, Parkinsonian symptoms, akathisia, dystonia, tardive dyskinesia, neuroleptic malignant syndrome, gynecomastia [enlarged breasts in men] and other sexual dysfunctions.” Tardive dyskinesia (TD), a movement disorder caused by antipsychotic drugs, is a major threat to children, according to Breggin. TD can effect any muscle functions that are wholly or partially under voluntary control. That includes the face, eyes, tongue, jaw, neck, back, abdomen, and more. Here are two videos of what TD looks like in a child. The first is a girl after she stopped taking her medications, presumably because of the TD. The second one is of another young girl trying to fall asleep.

Even ‘mild’ cases of eye blinking or grimacing can humiliate, stigmatize and isolate a child. More severe cases disable children with painful spasms in the neck and shoulders, abnormal posture and gait, or constant agitated body movements.

Additional concerns with the newer antipsychotics include a potential predisposition to heart disease and early death; weight gain and obesity; elevated blood sugar and diabetes; elevated blood lipids and atherosclerosis, and high blood pressure.

The New York Times published an article by Alan Schwartz, that looked at the growing practice of giving antipsychotics to children under the age of 2. His introductory case illustration was a boy who was first prescribed the antipsychotic Risperdal when he was 18 months of age. His mother indicated that she was never told of the potential risks to her son with Risperdal. “It was just ‘Take this, no big deal,’ like they were Tic Tacs,” said Genesis Rios. The prescribing doctor declined to be interviewed by the NYT.

Cases like that of Andrew Rios, in which children age 2 or younger are prescribed psychiatric medications to address alarmingly violent or withdrawn behavior, are rising rapidly, data shows. Many doctors worry that these drugs, designed for adults and only warily accepted for certain school-age youngsters, are being used to treat children still in cribs despite no published research into their effectiveness and potential health risks for children so young.

Schwartz reported that almost 20,000 prescriptions for antipsychotics such as risperidone (Risperdal) were written for children 2 years old and younger in 2014. This was a 50% jump from the year before. As a side note, prescriptions for the antidepressant fluoxetine (Prozac) rose 23 percent in one year for the same age group. A dozen experts in child psychiatry had never heard of children younger than 3 getting such medication and had difficulty explaining a reason for it. Dr. Martin Drell, a former president of the American Academy of Child and Adolescent Psychiatry said he was “hard pressed to figure out what the rationale would be.” Dr. Ed Tronick, a professor of developmental and brain sciences at the University of Massachusetts said:

I think you simply cannot make anything close to a diagnosis of these types of disorders in children of that age. . . . There’s this very narrow range of what people think the prototype child should look like. Deviations from that lead them to seek out interventions like these. I think it’s just nuts.

The American Academy of Pediatrics and the American Academy of Child and Adolescent Psychiatry have not taken a stand for or against the practice. They have no guidelines or position statements on the use of antidepressant or antipsychotics with children younger than 3. One possible factor in their silence is there are no formal trials in infants and toddlers with these medications. Dr. Mary Gleason a pediatrician and child psychiatrist at Tulane University School of Medicine said children with ages measured in months have brains whose neurological development was occurring at too rapid of a rate—and in still unknown ways—to risk using medications that could profoundly influence that growth. “There are no studies … and I’m not pushing for them,” said Dr. Gleason.

In an article for Psychiatric Services, psychiatrists at Dartmouth expressed concern about the increasing numbers of children being prescribed antipsychotic medications. In an article summarizing the concerns of the authors, Mad in America quoted them as saying:

The crux of the issue is this: Children in the United States have increasingly been prescribed antipsychotic medications despite potentially serious short- and long-term side effects. . . . Yet other efficacious and safer interventions are available. . . . We should be concerned about overuse of antipsychotics for many reasons. Children are inherently vulnerable because their brains and bodies are still developing and may be permanently altered by powerful medications. . . . Their disruptive behaviors are often related to disruptive parenting and stressful environments, which deserve primary attention. Adults may be motivated by the desire to achieve short-term control of behavior rather than to enhance children’s long-term growth and development.

Daviss et al. recommended five changes to reduce the use of antipsychotics in children. First, there is a need for preventive care that addresses socioenvironmental problems. Second, mental health professionals need to become more aware of the dangers of using antipsychotics in children as well as the availability of evidence-based therapies and interventions. Third, clinical guidelines need to be developed along with steps to ensure compliance with those guidelines. Fourth, there should be shared decision making when treating children with these medications. “Clinicians, patients, and parents all need better information on antipsychotics and should all be involved in deciding on appropriate treatment methods.” And fifth, education programs regarding these concerns are needed to reach the agencies and counselors who take care of and support vulnerable children.

Dr. Gleason commented that people are trying to do the best they can with the tools available to them. “There’s a sense of desperation with families of children who are suffering, and the tool that most providers have is the prescription pad.” These children and families deserve better than a choice between trying to cope with the behaviors they see their child struggle with, and using a chemical straitjacket with the potential of long-term cognitive and physiological harm.

02/26/16

Hollow Man Syndrome

25674445_sOn her blog Joanna Moncrieff reflected on a memory she has of a young woman she encountered as a medical student in the 1980s who was confused and frightened when first brought to the hospital. She thought she was being watched and manipulated by evil forces. She believed there was something implanted in her body. Put on an antipsychotic, she became increasingly quiet as the dose was increased. But she also became emotionless, expressionless and physically sluggish. To Joanna, the woman seemed “empty and lifeless compared to what she had been before, although she was less distressed.” This was seen as making her ‘better.’

That reminded me of a young man I knew briefly around the same time who had a psychotic episode, triggered by his heavy use of marijuana. At least, that was his theory. My impression of him after his release from the hospital, where he also began using an antipsychotic, was that his personality had withered; he’d become a hollow man. A few years ago, I met briefly with someone trying to reclaim their thinking ability after taking lithium for over fifteen years. They wanted to cut back on the levels of lithium they were taking. We began working on that plan, but they kept getting caught up in a cognitive eddy of fear that they were going to lose their salvation. Was that psychosis or impaired thinking from the medication?

Another time I was concerned that after a first time manic episode an adolescent would remain on a maintenance dose of an antipsychotic for the rest of his/her life.  Over time I convinced the family to transfer care to a psychiatrist willing to taper the teen off the antipsychotic. The person’s dose was initially halved and symptoms of mania emerged within ten to fourteen days of the initial taper. Was that a suppressed bipolar disorder emerging or was it a reaction to too steep an initial taper? The reaction was viewed by the family as a manifestation of the bipolar disorder that had been kept at bay by a low maintenance dose of the antipsychotic. They decided to stop counseling with me.

These and other experiences have led to the several articles I’ve written on the complications and dangers of antipsychotic medications. Reading the thoughts of psychiatrists like Joanna Moncrieff, Peter Breggin, and David Healy and others on Mad in America over the years had an effect as well. I appreciate the approach of Dr. Moncrieff, who said: “There are times when the use of antipsychotic drugs seems to produce just enough suppression that people can put aside their psychotic preoccupations, and re-establish a connection with the outside world.” Yet she can still see where “they produce an artificial state of neurological restriction,” like a chemical straightjacket.

In my view antipsychotic drugs can be useful in suppressing psychotic symptoms, and sometimes, when people are beset by these symptoms on a continual basis, life on long-term drug treatment, even with all its drawbacks, might be preferable to life without it. But most people who experience a psychotic breakdown recover. [Emphasis added] In this situation, antipsychotics are recommended not on the basis that they provide relief from severe symptoms, but because they are said to reduce the risk of relapse.

The Cochrane Collaboration published a review of antipsychotic maintenance treatment for schizophrenia in 2012. Their report was the first systematic review comparing the effects of all antipsychotic drugs to placebo for maintenance treatment. This is standard care after an acute phase of schizophrenia to prevent relapse. (And it seems, if a teenage manic episode is suspected of being a latent bipolar disorder) Not surprisingly, they found that antipsychotics were more efficacious than placebo in preventing relapse, especially at seven to 12 months. But they noted it was rare to find a study that did follow up longer than 12 months.

Randomised controlled trials (RCTs) since the 1950s have consistently shown that antipsychotic drugs effectively reduce relapses and need for hospitalisation. Conversely, they are, as a group, associated with a number of side effects such as movement disorders, weight gain and sedation.

Moncrieff pointed out two additional problems with these kinds of comparisons. First is the fact that they don’t compare people started on long-term medication treatment and people who were drug free in the placebo groups. Rather, the latter group consists of people who are withdrawn from long-term antipsychotics. Usually the taper or withdrawal occurs too quickly, precipitating discontinuation symptoms, like with the teen I described above. “The difference in relapse rates is almost certainly exaggerated in these studies, therefore, especially since relapse is often defined only in terms of a modest deterioration in general condition or symptoms.”

Another problem is there is typically little data in the studies on anything other than the so-called “relapse,” which is too loosely defined in most studies. So global functioning could be worse for people on continuous drug treatment than they would have been without it, even if they did experience a relapse. “Since the data has not been collected, we just don’t know.”

The first problem perpetuates a distorted message of how antipsychotic medications prevent relapse. The second problem means there is no information on whether someone might be better off if they didn’t use medication.

Moncrieff recently published an article in PLOS Medicine that called for a rethinking of antipsychotic maintenance: “Antipsychotic Maintenance Treatment: Time to Rethink?” Her summary points in the article were:

  • Existing studies of long-term antipsychotic treatment for people with schizophrenia and related conditions are too short and have ignored the impact of discontinuation-related adverse effects.
  • Recent evidence confirms that antipsychotics have a range of serious adverse effects, including reduction of brain volume.
  • The first really long-term follow-up of a randomised trial found that patients with first-episode psychosis who had been allocated to a gradual antipsychotic reduction and discontinuation programme had better functioning at seven-year follow-up than those allocated to maintenance treatment, with no increase in relapse.
  • Further studies with long-term follow-up and a range of outcomes should be conducted on alternatives to antipsychotic maintenance treatment for people with recurrent psychotic conditions.

She described a long-term randomized controlled trial (RCT) by Wunderlink et al. in the Netherlands (in this article as well as in her blog) that confirms how long-term antipsychotic use will impair a person’s ability to function. The study also showed that when you gradually reduce people’s antipsychotics in a supportive manner, they are better off in the long-term.

This study should fundamentally change the way antipsychotics are used. These are not innocuous drugs, and people should be given the opportunity to see if they can manage without them, both during an acute psychotic episode and after recovery from one. If psychiatrists had not forgotten the lessons of the past, and if they had been prepared to acknowledge what they saw the drugs doing with their own eyes, this would have come about long ago.

The studies used to justify current clinical practice don’t provide reliable data on the pros and cons of long-term antipsychotic therapy. More research is needed to evaluate the efficacy of a gradual and individualized approach to antipsychotic discontinuation. Assessment of outcomes in addition to relapse is needed. Moncrieff recommended that while we await the results of further long-term discontinuation studies, that we reconsider antipsychotic maintenance treatment as the default strategy for people with recurrent psychotic disorders.

In “Psychiatric Drug-Induced Chronic Brain Impairment,” Peter Breggin described how chronic brain impairment (CBI) from chronic exposure to psychiatric drugs produces effects similar to those from a traumatic brain injury. He drew a parallel of effects between electroshock treatment, closed head injuries from repeated concussions (like what was portrayed in the movie, Concussion), and long exposure to psychiatric drugs:

The brain and its associated mental processes respond in a very similar fashion to injuries from causes as diverse as electroshock treatment closed head injury from repeated sports-induced concussions or TBI in wartime, chronic abuse of alcohol and street drugs, long-term exposure to psychiatric polydrug treatment, and long-term exposure to particular classes of psychiatric drugs including stimulants, benzodiazepines, lithium and antipsychotic drugs.

He said that by recognizing CBI, clinicians can enhance their ability to identify individuals who need to be withdrawn from long-term psychiatric drug treatment. Most patients show signs of recovery from CBI early in the withdrawal process. “Many patients, especially children and teenagers, will experience complete recovery.” With others, recovery could take place gradually; sometimes over years. Even when recovery is incomplete, Breggin said most patients wish to remain on reduced medication or none at all.

The symptoms of this syndrome include (1) Cognitive deficits, often first noticed as short-term memory dysfunction and impaired new learning, and difficulty with attention and concentration; (2) Apathy, indifference or an overall loss of enjoyment and interest in life activities; (3) Affective dysregulation, including emotional lability, loss of empathy and increased irritability; (4) Anosognosia or a lack of self-awareness about these changes in mental function and behavior.

02/5/16

Wolves in Sheep’s Clothing

© Eros Erika | 123rf.com

© Eros Erika | 123rf.com

Atypical antipsychotics are now the largest-selling class of drugs in the U.S., accounting for more than $14.6 billion in annual sales by 2010. They are also the class of psychiatric drugs with the most negative side effects—and that’s saying something when you consider the others, namely antidepressants and anti-anxiety meds. Because schizophrenia effects such a small percentage of the population, the initial market for atypical antipsychotics was limited. The path to increased sales led through finding a wider market than just individuals with schizophrenia. So the pharmaceutical companies began to look at the behavioral disorders.

For the most part, these disorders are less serious than schizophrenia, but many are severe nonetheless, including hyper-activity in children and agitation in elderly patients. Marketing atypical anti-psychotic agents to patients with this broader category of disorders held the promise of sales reaching blockbuster levels.

There were two obstacles to this broader promotion. First, the FDA had only approved atypicals for the treatment of severe psychosis—schizophrenia—in adults. Their use for other disorders was then off-label. FDA regulations prohibit pharmaceutical companies from promoting drugs for such additional uses.

The second obstacle was that they didn’t have a very good safety profile. Used for a serious disorder like schizophrenia, the adverse effects of atypicals were understood to be a trade off. “But the risk–benefit calculus is much less favorable when milder conditions are involved.” Despite these impediments, the temptation was too much for the manufacturers to resist and a number of lawsuits over the past few years attest to this. Read “Antipsychotic Medications Are Spelling Legal Trouble for Drugmakers” for more information on this. Robert Field concluded his article with this observation:

 In light of the large number of successful enforcement actions and the continued potential for abuses, prosecutors are likely to remain vigilant concerning the marketing of atypical antipsychotic agents. Repeated violations could generate even larger penalties. Publicity over the large settlements has put physicians and the public on notice about the hazards of indiscriminate use of this class of drugs. In the future, regulators, clinicians and patients should view atypical antipsychotics and marketing claims concerning them with caution.

Over time, antipsychotics have “evolved.” Some are now approved as adjunct medication for treating major depression. Many are now are also prescribed for the treatment of bipolar disorder. And then there is off-label market for several behavioral disorders. No longer are they relegated to just the niche market of people diagnosed with schizophrenia.

The FDA-approved uses for antipsychotics now include the treatment of bipolar I disorder, schizophrenia, schizoaffective disorder and as an adjunct treatment for major depression. In addition to their FDA approved uses, several atypicals are used off-label to treat various psychiatric conditions. They have been studied as off-label treatment for the following conditions: ADHD, anxiety, dementia in elderly patients, depression, eating disorders, insomnia, OCD, personality disorder, PTSD, substance use disorders, and Tourette’s syndrome.

Clozapine (Clozaril) was the first atypical developed. Introduced in Europe in 1971, it was voluntarily pulled by its manufacturer when it was shown to cause a condition called agranulocytosis, a dangerous decrease in the number of white blood cells. It was then approved by the FDA in 1989 for the treatment of treatment-resistant schizophrenia. In 2002 the FDA also approved clozapine for reducing the risk of suicidal behavior. However, the FDA also requires it to carry five black box warnings for a series of adverse health effects including cardiovascular and respiratory problems and increased mortality in elderly patients with dementia-related psychosis.

The five main atypical antipsychotics currently used in the US are: Aripiprazole (Abilify), Olanzapine (Zyprexa), Quetiapine (Seroquel), Risperidone (Risperdal) and Ziprasidone (Geodon).  There are six newer ones whose off-label use have not been documented or researched as extensively as the preceding five have been. These newer ones are: Asenapine (Saphris), Iloperidone (Fanapt), Lurasidone (Latuda) and Paliperidone (Invega). Two brand new antipsychotics, Rexulti (brexpiprazole) and Vraylar (cariprazine), will be discussed below.

There are also six other atypicals that have not been approved for use in the US. They are: Amisulpride, Blonanserin, Melperone, Sertindole, Sulpride and Zotepine.  The following chart lists the FDA-approved indications for atypical antipsychotics.

Atypicals

Bipolar 1

schizophrenia

schizoaffective

Major depression

Aripiprazole

yes

yes

yes

Olanzapine

yes

yes

yes

Quetiapine

yes

yes

yes

Risperidone

yes

yes

Ziprasidone

yes

yes

Asenapine

yes

yes

Iloperidone

yes

Lurasidone

yes

yes

Paliperidone

yes

yes

Clozapine

yes

yes

Brexpiprazole

yes

yes

Cariprazine

yes

yes

Schizophrenia is the primary disorder for which antipsychotics are targeted and bipolar 1 disorder is second. Three of the main antipsychotics have been approved as augmentations for antidepressants, Aripiprazole, Olanzapine and Quetiapine. Interestingly, the medication guides for most of the antipsychotics seem to downplay the drug class they are in. They only refer to themselves as “antipsychotic” within the warning of a potential side effect called neuroleptic malignant syndrome. Coincidentally, that is the only place the other common term for antipsychotic, neuroleptic, is found.

Here is an example of how the warning for the potential side effect of neuroleptic malignant syndrome: was worded for Seroquel (quetiapine): “neuroleptic malignant syndrome (NMS). NMS is a rare but very serious condition that can happen in people who take antipsychotic medicines, including SEROQUEL.” Many of the other antipsychotics have similar wording for the discussion of this side effect. Abilify never refers to itself as an antipsychotic or neuroleptic in its medication guide. Under the discussion of possible side effects with Abilify is the following:

 Neuroleptic malignant syndrome (NMS): Tell your healthcare provider right away if you have some or all of the following symptoms: high fever, stiff muscles, confusion, sweating, changes in pulse, heart rate, and blood pressure. These maybe symptoms of a rare and serious condition that can lead to death. Call your healthcare provider right away if you have any of these symptoms.

But you will find a lot of discussion about antidepressants in some of these medication guides. Many of the antipsychotics use language that gives the impression that the drug is an “antidepressant,” not an “antipsychotic.” The medication guides for Abilify (aripiprazole), Seroquel (quetiapine) and Latuda (lurasidone) have an entire section that discusses what someone needs to know about antidepressant medications. Someone not familiar with the various classes of medications who are taking these drugs might think they are taking antidepressant and not an antipsychotic.

The following table summarizes the evidence for off-label use of the five primary atypical antipsychotics currently used in the US are: Aripiprazole, Olanzapine, Quetiapine, Risperidone and Ziprasidone. The strongest evidence of efficacy is noted as “++”, then “+”.  “0” means there have been no clinical trials attempted; “-“ represents no efficacy and “+-“ is for mixed results. “FDA” represents FDA approval for the condition. Keep in mind these ratings are based upon the data from the drug companies in their quest to expand the antipsychotic market.

Disorder

Aripiprazole

Olanzapine

Quetiapine

Risperidone

Ziprasidone

Anxiety

0

++

ADHD

0

0

0

+

0

Dementia

++

+

+

++

0

Depression

FDA

FDA

FDA

++

+

OCD

0

+

++

PTSD

0

+-

+-

++

0

Tourette’s

0

0

0

+

Risperidone was the first of the main five antipsychotics brought to market in 1990 by Janssen. In 1996 Eli Lilly brought olanzapine to market in September of 1996 and AstraZeneca brought quetiapine to market in September of 1997. Pfizer brought ziprasidone to market in June of 2002 and Bristol-Myers Squibb had aripiprazole approved in November of 2002.  All five are currently off patent. The patent expiration dates for the newer antipsychotics are as follows: Asenapine (Saphris) in 2020, Iloperidone (Fanapt) 2027, Lurasidone (Latuda) 2018. Paliperidone (Invega) lost its exclusivity on October 6, 2014.

Two brand new antipsychotics, Rexulti (brexpiprazole) and Vraylar (cariprazine) were just approved by the FDA in the summer of 2015.  Vraylar was approved for the treatment of schizophrenia and bipolar disorder in adults. Rexulti was approved as a treatment for schizophrenia and as an add-on treatment for adults with major depression.

The Rexulti medication guide also has a section describing what you need to know about antidepressants. It has the same warning for the potential side effect of neuroleptic malignant syndrome (NMS) found with Abilify. It also lists major depression as the first disorder it is used to treat; schizophrenia is listed second. So it seems that it is positioning itself to be seen more a treatment for depression than schizophrenia.

To its credit, Vraylar’s medication guide regularly refers to antipsychotics and the side effects of antipsychotics. And I did not find even ONE reference to “antidepressant.” However, its discussion of NMS is subtle, never explicitly saying it could occur from Vraylar. Under warnings and precautions it says:

Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

However, truth in advertising isn’t the only concern, at least with Vraylar. Johanna Ryan described a detailed investigation she did of the Vraylar studies registered with ClinicalTrials.gov. Out of the twenty registered studies, seventeen were completed, but still had not shared their results on the government website, a mandatory step in the process. I reviewed all the registered studies for Vraylar on December 4, 2015 and there were still no posted results from the completed clinical trials for Vraylar almost two months after Ryan’s article was posted on davidhealy.org.

She found at least six published papers directly based on these studies; only two were posted on CT.gov. The average number of listed authors was six to eight, with an academic noted as the “lead” author. The rest were drug company employees. Some papers only had employee-authors.

Overwhelmingly they were contract researchers. Some were freestanding clinical trial businesses. Others were busy medical practices with a thriving research business “on the side.” The first recruited subjects largely by TV, newspaper and online advertising which emphasized free treatment. The second combined some advertising with recruitment among their own patients.

The adverse side effects with antidepressants are increasingly evident, as is their well-documented ineffectiveness. But they are more acceptable by our cultural psyche than antipsychotics. Remember Listening to Prozac? Antipsychotics (neuroleptics) are now the “it” class of psychiatric medications. As they expand their market reach to beyond schizophrenia, the term “antipsychotics” has become a liability for sales. “Anti “depression” medication is an easier sell than anti “psychotic.” So it seems there has been an intentional effort by some pharmaceutical companies to blur the lines between the drug classes of antidepressants and antipsychotics.

I think a fitting metaphor for what’s happening is to think of this marketing strategy as an attempt to pass off wolves in sheep’s clothing. But you have to wonder just how bad the adverse effects of antipsychotics  (the wolves) are when the less harmful half of the metaphor—the “sheep”—is antidepressants.