01/13/17

Iatrogenic Gun Violence

© StephanieFrey | stockfresh.comfresh eggs. Araucanas are also known as the Easter Chicken for the blue or greenish colored eggs they lay.

Whenever I read about horrific violence like the incident in the Fort Lauderdale airport, I wonder what role psychiatric medications played. I wonder if the violent behavior was iatrogenic—was it caused by psychiatric medications? This question will sound counter intuitive for many people. Surely the reverse is true. Psychiatric medication and proper diagnosis should have prevented it. Let’s see if it is.

Esteban Santiago was deployed to Iraq from April 2010 to February 2011 with the 130th Engineer Battalion, the 1013th Engineer Company of the Puerto Rico National Guard. After flying from Alaska to Fort Lauderdale Florida, he retrieved his baggage, which incidentally contained a semi-automatic handgun. Santiago had followed proper protocol, checking the weapon with TSA. He went into the men’s bathroom, loaded his weapon and opened fire in Terminal 2 of the airport, killing five people and wounding six others. A witness said he was just randomly shooting people, with no rhyme or reason to it.

Family members reported that he was a changed man when he returned from Iraq. His aunt said his mind was not right. At times he seemed normal, but other times he seemed lost. In Iraq, his unit cleared roads of improvised explosive devices and maintained bridges. Two people in his unit died while he was in Iraq. His aunt said: “He talked about all the destruction and the killing of children. He had visions all the time.” He had changed.

His brother Bryan confirmed that recently Esteban was hallucinating, but said he was receiving psychological treatment. Bryan said he believes the shooting rampage resulted from mental issues that surfaced after the Iraq tour. When Esteban’s tour ended, he was hospitalized for mental problems. Upon his release, he went to Puerto Rico where his father was ill and eventually died. While in Puerto Rico, he received mental health therapy. Esteban eventually moved to Alaska, where he joined the Alaska National Guard in November 2014. He was discharged in August of 2016.

Over the course of 2016, Santiago was repeatedly reported to Anchorage police for physical disturbances. In January of 2016 he was arrested and charged with assault and criminal mischief after an argument with his girlfriend. He allegedly yelled at her while she was in the bathroom and broke down the bathroom door. She told investigators that he tried to strangle her and struck her on the side of the head.

Santiago pleaded no contest to criminal mischief and assault charges. Under a deferred prosecution agreement, his charges would have been dismissed if he complied with the conditions. He was due back in court on March 28th, 2017 to assess his progress.

While living in Alaska, Esteban continued to receive psychological treatment, according to his brother. Although his girlfriend alerted the family to the situation in Alaska, Bryan said he did not know what mental health problem Esteban was being treated for; they never spoke about it by phone.

His son was born in September of 2016. In November of 2016, Esteban walked into an FBI office in Anchorage to report that his mind was being controlled by a U.S. intelligence agency. He told officials he had a firearm in his car, along with his newborn son. Santiago was checked into a mental health facility; his firearm was logged as evidence for safe keeping. The infant’s mother came for their child. FBI special agent Marlin Ritzman said:

During the interview, Mr. Santiago appeared agitated, incoherent and made disjointed statements. Although he stated he did not wish to harm anyone, as a result of his erratic behavior our agents contacted local authorities, who took custody of Mr. Santiago and transported him to the local medical facility for evaluation.

After conducting database reviews, interagency checks and interviews with his family members, the FBI closed its assessment of Santiago. Agents found no ties to terrorism during their investigation. A CNN senior law enforcement analyst and former FBI assistant director said Santiago hadn’t been adjudicated a felon and he hadn’t been adjudicated as mentally ill. So they couldn’t keep his weapon. The Walther 9-millimeter pistol was returned to him in the beginning of December. Authorities told CNN it was the pistol he used in the shooting incident in Fort Lauderdale.

Typically, Esteban was considered to be a calm young man who was never violent. Recently he began selling his possessions, including his car. Friends and associates noticed more erratic behavior. He bought a one-way ticket to Fort Lauderdale and packed his pistol and two magazines. His carryon bag with the pistol was his only luggage. He flew from Anchorage to Minneapolis to Fort Lauderdale. He retrieved his bag from the baggage claim area and went into a men’s room stall to load his pistol.

He shot the first people he saw, going up and down the carousels of the baggage claim, shooting through luggage to get at people that were hiding. He thinks he fired 15 bullets, aiming at his victim’s heads. A witness said Esteban showed no remorse. He didn’t say anything. “No emotion, no nothing. About as straight-faced as you get.” Afterwards, he just lay face down, spread eagle, waiting for the deputies to come and get him.

The above report was pieced together from information contained in the following reports by The New York Times here,  NJ.com here, CNN here, and NPR here.

There was no explicit mention of Santiago’s repeated involvement in “psychological treatment” involving psychiatric medications, but it highly probable he was taking psychiatric medication of some sort. The lack of any mention of his being prescribed medication may simply be due to confidentiality regulations. Or this silence could be due to the chicken-and-egg argument often applied to incidents involving violence and individuals with known psychiatric problems. Their mental illness, not the drugs to treat it, caused their horrific behavior.

Several psychiatrists have voiced concerns with psychiatry, its over reliance upon medication and denial of serious adverse effects from medication, like violence and suicide. Joanna Moncrieff said she’s sad her profession has not taken the harms drug treatments can do more seriously. She said it has a long history of ignoring the adverse effects of drugs, or attributing them to the underlying disease—of blaming the patient instead of the drug. “Too many psychiatrists have just accepted that drug treatments are good, and have not wanted to contemplate that actually these treatments could be harmful.”

First and foremost, she said, psychiatry needs to adopt a drug-centered model for understanding its drug treatments and what they do to people. Psychiatrists need more information, knowledge and training on what the drugs do—what effects they produce in people; “how they change the way that people think and feel and what sort of impact those changes have on people’s lives.” Watch two brief videos of her expressing her concerns here. You can read more about her “drug-centered model” here on this website: “A Drug is a Drug is a Drug.”

Peter Breggin has raised concerns with the association of violence and antidepressants since the early days of Prozac. In his 1991 book, Toxic Psychiatry, Dr. Breggin related newspaper and scientific reports pointing to an association between Prozac and “compulsive, self-destructive and murderous activities.” He said then he was personally familiar with several cases of compulsive suicidal or violent feelings that developed after taking Prozac. Over the years, his familiarity grew.

In “Psychiatry Has No Answer to Gun Massacres,” Breggin described how the Columbine High School shooter, Eric Harris had a “therapeutic” level of Luvox (fluvoxamine) in his body at the time of the murders.  He had a dose increase in his medication 2 ½ months before the assault and showed signs of drug toxicity five weeks before the event. James Holmes, the Aurora Colorado theater shooter, was in psychiatric treatment with the medical director of student health services, who was considered an expert on campus violence. She was concerned enough about Holmes to report him to the campus police and the campus threat assessment team a few weeks before the assault. When the assessment team suggested putting him on a 72-hour involuntary hold, she rejected the idea. “When Holmes quit school, the school washed its hands of all responsibility for him.”

In a 2010 journal article, “Antidepressant-Induced Suicide, Violence, and Mania: Risks for Military Personnel,” Dr. Breggin related how the adverse effects described in the 2009 edition of the Physicians’ Desk Reference for Zoloft (sertaline) resembled the most frequent psychiatric disorder associated with combat—PTSD—with its hyperalert overstimulated symptoms. He said identical or nearly identical warnings can be found in all antidepressant labels. “All these potentially dangerous symptoms are also commonly seen in PTSD in military personnel, posing the risk of worsening this common military disorder.”

Looking at the revised 2016 medication guide for Zoloft, we see that nothing much has changed with regard to adverse effect warnings. It said Zoloft and other antidepressant medications could increase suicidal thoughts or actions. Symptoms needing immediate attention included: acting aggressively or violent, feeling agitated, restless angry or irritable, an increase in activity or talking more than what is normal, acting on dangerous impulses, trouble sleeping, new or worse anxiety or panic attacks, trouble sleeping, other unusual changes in behavior or mood.

A condition known as “serotonin syndrome” has symptoms such as: agitation, hallucinations, coma and other changes in mental status. Symptoms of potential manic episodes included: greatly increased energy, racing thoughts, unusually grand ideas, severe trouble sleeping’s, reckless behavior, excessive happiness, talking more or faster.

Dr. Breggin concluded his article with the following cautions and recommendations. He said there was a strong possibility the increased suicide rates among active-duty soldiers were in part caused or made worse by the widespread prescription of antidepressant medication. Alone, they can cause a stimulant-like series of adverse effects. “These symptoms of activation can combine adversely with similar PTSD symptoms found so commonly in soldiers during and after combat.” He recommended the military study the relationship between psychiatric drug treatment and suicide as well as random or personal violence. He also suggested that antidepressants should be avoided in the treatment of military personnel.

Another emerging concern of an association between antidepressants and violence is in the research done by Yolande Lucire. She suggested that mutations in CYP450-encoding genes contributed to problems metabolizing psychiatric drugs, and thus were contributing factors in three cases of antidepressant-induced akathisia-induced homicide. The cytochrome P450 family of enzymes is responsible for metabolizing most of the drugs used in psychiatry. You can read her article here. You can also find another article: “Psych Drugs and Violence” on this web site. Within that article you will find a link to another article by Lucire on antidepressant-induced akathisia-related homicide and the CYP450 genes.

Hasn’t there been enough evidence associating suicide and violence with psychiatric medications, especially antidepressants, for open dialogue and more comprehensive scientific research into this public health issue? How many more Columbines, Auroras and Fort Lauderdales need to happen before we begin to address the association of psychiatric drugs and violence?

07/12/16

Common Sense with Lithium

© Suljo | stockfresh.com

© Suljo | stockfresh.com

Lithium carbonate (not the element lithium) is used as a psychiatric medication primarily with bipolar disorder. It can be used with other psychiatric disorders such as major depression and schizophrenia, when first line medications are not effective. There are several advantages to lithium, particularly when it comes to cost. Available as a generic medication, a typical daily dose costs between 90 cents and $1.20. Major downsides are that therapeutic doses are just lower than toxic doses and there is the potential of direct damage to the kidneys and thyroid.

The website drugs.com said that since the toxic levels for lithium are so close to the therapeutic levels, patients and their families should watch for early symptoms, then discontinue the drug and inform the physician should they occur. Indications of lithium toxicity may include: diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination. There are a host of other potential side effects that include: confusion, dry mouth, muscle twitching or trembling, vertigo, increased urination, memory problems and weight gain. These are only a few of the side effects found in 10% or more of the persons using lithium. See drugs.com or the Wikipedia listing for a more detailed discussion of lithium side effects.

In the late 1800s lithium was a popular ingredient in elixirs and tonics. It was even added to beer and other beverages. The theory was that it dissolved uric acid, so it could break up kidney stones and the uric acid crystals associated with gout. It was found to have no such effects. Lithium was eventually banned by the FDA in 1949 when it was found to cause cardiovascular problems.

Coincidentally, that same year an Australian physician named John Cade published a paper describing his treatment of 10 patients with mania with lithium. Cade had noticed that lithium made guinea pigs docile, so he thought it could have a therapeutic effect in manic patients. He announced dramatic effects in his paper and claimed they were specific to mania. What he failed to mention was that one patient died, two others had to discontinue lithium because of severe toxicity and one patient refused to take it. None of this was reported in his paper. Side effects were noted 41 times in the clinical records, but only 1 time in the published article. See The Myth of the Chemical Cure by Joanna Moncrieff for a more detailed description of lithium as a psychiatric treatment.

In Anatomy of an Epidemic, Robert Whitaker noted that psychiatrists in the U.S. had little interest in lithium until manic-depression was distinguished into unipolar and bipolar forms. Only a few placebo-controlled trials of lithium had ever been done up to that point. In 1985 UK researchers could only identify four with any merit. But within those studies, lithium was said to have a good response rate in 75% of the patients. This was much higher than the response rate in the placebo group.

A 1994 meta-analysis of nineteen studies by J.P. Baker of patients who were on lithium and had their lithium withdrawn showed that 53.7% of the patients relapsed, versus 37.5% of the lithium-maintained patients. This was seen as clear evidence that lithium prevented relapse. However, only 29% of patients who were gradually withdrawn from lithium relapsed. Note how this rate was better than those in the drug-maintained group.

Whitaker said this wasn’t very robust evidence of lithium’s benefit to patients, especially when you considered the additional studies raising concerns about lithium’s long-term effects. There was also a high rate of patients who stopped taking lithium—over 50%—because of how the drug dulled their minds and slowed their physical movements. In 1999 Baldessarini et al. found that almost half of all patients relapsed within five months of quitting lithium, while individuals who did not use lithium took nearly three years to reach that percentage of relapse. “The time between episodes following lithium withdrawal was seven times shorter than it was naturally.” Whitaker noted:

Although lithium is still in use today, it lost its place as a first-line therapy once “mood stabilizers” were brought to market in the late 1990s.

Now there has been a growing body of evidence that suggests lithium prevents suicide. In 2003 Baldessarini and others found that long-term lithium maintenance patients had lower suicide rates than individuals who did not. Cipriani et al. found lithium was an effective treatment for reducing the risk of suicide in people with mood disorders as well as bipolar disorder. Lewitzka et al. did a comprehensive review of more than 20 years of studies investigating the anti-suicide effect of lithium in patients with affective disorders. They also concluded lithium to be “an effective treatment for reducing the risk of suicide and suicide attempts in patients with affective disorders over the long-term course.”

Joanna Moncrieff reviewed several meta-analyses indicating the anti-suicide effects of lithium in The Myth of the Chemical Cure and said the studies included in these analyses had conflicting results. An article on her website, “Lithium and Suicide: What Does the Evidence Show?” said the proposed effect of decreased mortality rates was inexplicable since lithium was a toxic drug that made most people feel rather depressed. She wondered if the sedating effect of the lithium sapped people of the will to act. “A closer look at the evidence, however, suggests the idea [lithium reducing suicidality] is simply not justified.”

The first issue was that the evidence supporting this idea consisted of follow-up studies with individuals on long-term lithium, as with Copper et al. Moncrieff commented how these people are a particularly compliant group with medication. “People who follow their lithium regime religiously are, in general, not likely to be the people who are chaotic, impulsive, desperate and most likely to commit suicide.” One study, by Gonzalez-Pinto et al., showed that people who were highly compliant with their lithium were five times less likely than those who were ‘poorly compliant’ to commit suicide. A second issue was that given small margin of error between therapeutic and toxic doses of lithium, people with suicidality tendencies are less likely to be given lithium.

Another confounding issue is that people with medical conditions are less likely to be given lithium. Not only can lithium cause kidney and thyroid problems, but it interacts with many commonly prescribed drugs like diuretics, ACE inhibitors and NSAIDS like aspirin and ibuprofen. This can result in dangerously high lithium levels. So caution is used when starting lithium with someone who is physically sick or taking other medication. Moncrieff said better randomized controlled trials are needed.

She thought it curious that a meta-analysis by Cipriani et al. in 2013 did not include a single placebo-controlled trial where the suicide rate was zero, so she looked more closely at its methology. Moncrieff discovered that the authors excluded any trial whose treatment arm was uninformative, namely those whose suicide rates were zero. “This decision is totally unsound, however, as it reduces the denominator (the total number of participants) and thereby makes the events included appear more common than they actually were.” She speculated this was why some well-known studies were not included in the analysis of suicides. When the studies with no suicides were included, “the number of participants would have been much larger and the proportion of suicides in the placebo group much smaller.”

 So there is the evidence on lithium and suicide. The meta-analysis that has been accepted as demonstrating that lithium prevents suicide spuriously inflated the suicide rate on placebo by excluding studies in which no suicides occurred. The only double blind, prospective study designed to test whether lithium reduces suicide in people at high risk, ended up unblinding many of its participants, and in any case suicidal events were low in both groups.

The fact that studies of suicide prevention have been so difficult to recruit to, suggests patients may have more sense than researchers in this field!

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.

09/2/15

Do No Harm with Antidepressants

© Jrabelo | Dreamstime.com

© Jrabelo | Dreamstime.com

In April of 2006, I first read Irving Kirsch’s 2002 article, “The Emperor’s New Drugs.” In that article, Kirsch described how 80% of the response to antidepressant medications was duplicated in placebo control groups. Kirsch’s analysis was of the very same clinical data submitted to the FDA between 1987 and 1999 for the approval of 6 widely prescribed antidepressants. The allusion to Hans Christian Andersen’s tale, “The Emperor’s New Clothes” was fitting. Kirsch played the role of the little boy in Andersen’s tale to my understanding of how antidepressants work. He pointed to antidepressants and said: “But they have little or no therapeutic effect at all!”

Since 2006 I’ve become familiar with the work of several individuals questioning the received wisdom of psychotropic medications, including Joanna Moncrieff. Her book, The Myth of the Chemical Cure, had its own “aha!” moment in the development of my thinking on the clinical use of psychiatric medications. A search of  “Faith Seeking Understanding” by their names will pull up other articles where I have referenced them.

Not too long ago, I saw a link to a new article by Joanna Moncrieff and Irving Kirsch, “Empirically derived criteria cast doubt on the clinical significance of antidepressant-placebo differences.” I’ve read previous articles written by Moncrieff and Kirsch, “Efficacy of antidepressants in adults” and “Clinical trials and the response rate illusion.” But still looked forward to reading their latest. It seems to have hammered home the final nail in the coffin of the ineffectiveness of antidepressants for me.

In “The Emperor’s New Drugs,” Kirsch found that the drug/placebo difference was less than 2 points on the Hamilton-D (HAM-D) scale, a scale often used in studies for assessing the effects of antidepressants. Even then, Kirsch et al. were saying that: “the clinical significance of these differences is questionable.” The spin put on his conclusions was that this was only to hold true only for individuals with mild cases of depression. Moderate to severe depression should still have antidepressants as a first-line treatment.

However, in “Efficacy of antidepressants in adults,” Moncrieff and Kirsch pointed out that the studies included in “The Emperor’s New Drugs,” were mainly with patients suffering with severe to very severe depression. They cited additional studies questioning the efficacy of antidepressants and concluded: “Recent meta-analyses show selective serotonin reuptake inhibitors have no clinically meaningful advantage over placebo;” and that “Claims that antidepressants are more effective in more severe conditions have little evidence to support them.”

In their most recent article, Moncrieff and Kirsch tackled the issue of how antidepressants have been shown to be statistically superior to placebo. This statistical significance has been true from the time of Kirsch’s work on “The Emperor’s New Drugs, ” where the authors said that: “Although mean differences were small, most of them favored the active drug, and overall, the difference was statistically significant.” Moncrieff and Kirsch commented that a three-point difference on the HAM-D scale could not be detected by clinicians. Clinically relevant drug-placebo differences would have to be 7 points or greater on the HAM-D scale. “Currently, drug effects associated with antidepressants fall far short of these criteria.”

These conclusions were built upon the work of German psychiatrist Stefan Leucht and his colleagues. You can read a less technical discussion of the importance of this research in Dr. Moncrieff’s blog, here. She said that a reduction of 2 points on the 52 point HAM-D scale, while statistically significant, seemed to be an insignificant amount. “Leucht et al. provide some empirical evidence to support that hunch.”

Given that there was little if any difference in clinically relevant effects between one treatment and another, Moncrieff and Kirsch suggested that patients and healthcare providers should be aware that all treatments, including placebo, produce some positive effect on symptom scales, “while none outperforms a pill placebo to a meaningful degree.”

The small differences detected between antidepressants and placebo may represent drug-induced mental alterations (such as sedation or emotional blunting) or amplified placebo effects rather than specific ‘antidepressant’ effects. At a minimum, therefore, it is important to ascertain whether differences correlate with clinically detectable and meaningful levels of improvement.

So where does this discussion lead us? Treating depressive symptoms with antidepressants should not be a first option. “Given the choice, most depressed patients prefer psychotherapy over medication.” Moncrieff and Kirsch suggest that decisions about treatment should include patient preference, safety and cost. With regard to safety, antidepressants should be a last choice for treatment alternatives.

Their article referenced a study by Andrews et al., “Primum non nocere” (first, do no harm), which noted a series of harmful effects from SSRIs. Serotonin has wide reaching effects on adaptive processes throughout the body and could have many adverse health effects. They described how antidepressants effect the proper functioning of homeostatic mechanisms in the body.  Long-term use is associated with a loss of symptom reducing effectiveness with SSRIs. This suggests that the brain is pushing back against the effects of SSRIs and trying to regain the homeostasis present before the use of antidepressants began. “Because of the complex role that serotonin plays in shaping the brain, antidepressants could have complex effects on neuronal functioning.”

Additional negative side effects included attention problems, driving performance, falling and bone fractures in the elderly, gastrointestinal problems such as diarrhea, constipation and irritable bowel syndrome. SSRIs may increase the risk of abnormal bleeding. They can related to an increase risk of cardiovascular events. There is concern that SSRIs can effect neonatal development. One study suggested SSRI use during pregnancy, especially the first trimester, led to an increased risk of Autism Spectrum Disorders. Andrews et al. summarized their findings here:

We have reviewed a great deal of evidence of the effects of antidepressants on serotonergic processes throughout the body. Some of the effects are widely known, but they have been largely ignored in debates about the utility of antidepressants. Indeed, it is widely believed that antidepressant medications are both safe and effective; however, this belief was formed in the absence of adequate scientific verification. The weight of current evidence suggests that, in general, antidepressants are neither safe nor effective; they appear to do more harm than good.

08/26/15

The Elephant in the Room

© tiero | 123rf.com

© tiero | 123rf.com

In 2006, Joanna Moncrieff asked why it was so difficult to stop psychiatric drug treatment? Received wisdom had answered that the difficulty arises from the underlying illness manifesting itself as the therapeutic effects of the medication becomes weaker. This presumes that the medications have disease-specific actions; that there is a disease-centered model of psychotropic drug action. But what if it had nothing to do with the original problem? Moncrieff suggested that problems experienced after psychiatric drug withdrawal were often related to the withdrawal process rather than the underlying condition. “If this is the case, then the recurrent nature of psychiatric disorders may be partially attributable to the iatrogenic effects of psychiatric drugs.”

She reviewed several case study examples to illustrate this concern and then indicated there were two possible mechanisms for withdrawal related disorders from this evidence. First, there were pharmacodynamic adaptations that took place. Long-term use of drugs that suppresses particular neurotransmitters (like serotonin in SSRIs) seems to cause an increase in number or a supersensitivity of the relevant receptors. When the receptors are no longer influenced by the drug, there is an over-activation of the neurotransmitter system—a rebound effect.

This may result in the characteristic discontinuation syndromes, may cause rapid onset psychosis and may act a source of  ‘‘pharmacodynamic stress,’’ which increases vulnerability to relapse.

A psychological reaction to the medication withdrawal, either by others or the patient, can also trigger symptoms or increase the patient’s vulnerability to relapse. Moncrieff said: “In my experience, psychological reactions by patients, staff and carers are important determinants of the success or failure of drug discontinuation, a proposition that is open to empirical testing.”

Moncrieff seems to be suggesting two things here. First, the importance of recognizing that post withdrawal symptoms will occur when a drug is tapered or stopped. Second, the importance of a system of support to the person seeking to successfully taper or stop their medications. Both of these factors are well known to anyone attempting to establish and maintain abstinence from addictive substances.

Along with David Cohen, Jonna Moncrieff suggested that we rethink our models of psychotropic drug action in their 2005 article. They noted the predominant “disease-centered model” of drug action that presumed psychiatric medications worked by acting on a specific disease process. In contrast, they suggested a “drug-centered model” that focused on the physiological, behavioral and subjective effects of the drug. Here, the therapeutic value of a drug stemmed from the usefulness of its effects in clinical situations. There is no presumption that it corrects some biological abnormality.

Moncrieff has also presented the differences between the disease-centered and the drug-centered models of drug action in her book, The Myth of the Chemical Cure. Moncrieff and Cohen used the distinction in a 2006 article, “Do Antidepressants Cure or Create Abnormal Brain States?” Applying the disease-centered model to antidepressants, they said:

Modelled on paradigmatic situations in general medicine—such as the use of insulin in diabetes, antibiotics in infectious disease, chemotherapy in cancer—the disease-centred model suggests that antidepressants help restore normal functioning by acting on the neuropathology of depression or of depressive symptoms.

Instead they proposed the drug-centered model was a better explanation for the observed drug effects in psychiatric conditions. “Instead of relieving a hypothetical biochemical abnormality, drugs themselves cause abnormal states, which may coincidentally relieve psychiatric symptoms.” After completing their analysis, they suggested that the term “antidepressant” should be abandoned, as the drugs were not treating a specific disease state.

Our analysis indicates that there are no specific antidepressant drugs, that most of the short-term effects of antidepressants are shared by many other drugs, and that long-term drug treatment with antidepressants or any other drugs has not been shown to lead to long-term elevation of mood.

This then brings us to “the elephant in the room”: a frank discussion on “The Psychoactive Effects of Psychiatric Medication” by Moncrieff, Cohen and Porter. They said when viewing the influence of psychiatric medications through the disease-centered model of action, their psychoactive effects have been obscured. “Despite six decades of intensive research in neuropharmacology … there is a lack of evidence that psychiatric drugs have a disease-specific action independent of their demonstrable psychoactive effects.” Approaching psychotropics as drugs that produce immediate and delayed psychoactive effects, with tolerance and dependence suggests that a radical change of thinking is needed.

Lessons from the use and misuse of other psychoactive substances can help to enlighten us about the broad range of behavioral effects that different psychiatric medications are likely to exert, and how these effects might interact with the psychological, behavioral, and other problems we call mental disorders.

Individuals who are prescribed psychiatric medications in this manner should be treated as consumers, “rather than passive recipients of diagnosis-driven prescribing.” The subjective experience of the individual would guide the use of psychiatric medications in a “collaborative dialogue” with the prescriber—rather than changes in symptoms or clusters of symptoms. “Only when we appreciate the nature of psychiatric drugs as psychoactive substances can we start to accumulate the knowledge necessary to enable prescribers and consumers to use these drugs safely and effectively.”

I heartily agree that we need to promote a drug-centered model of psychiatric drug action. However, additional changes will need to be made. Otherwise, the consumer-driven marketing model—“Ask your doctor if “X” is right for you”—will continue largely unchanged. Direct to the consumer advertising by Pharma will have to stop. Changes in how pharmaceuticals are approved though the FDA will have to occur. Better methodologies need to be developed for the approval process.

Transparency in pharmaceutical research needs to become the norm. Closer scrutiny into the potential harm and negative side effects has to occur, including long-term negative side effects. The psychoactive effect of drugs and its potential as negative side effect in all pharmacological products has to be weighed equally with the potential therapeutic benefit.

11/5/14

A Drug is a Drug is a Drug

The modern understanding of what drugs do in psychiatry, the basis of psychopharmacology, is fatally flawed.” (Joanna Moncrieff)

In The Myth of the Chemical Cure, British psychiatrist Joanna Moncrieff persuasively argued that believing modern drug treatments are specific cures for specific illnesses “is just as mistaken as the belief that insulin coma treatment was an effective and specific treatment for schizophrenia.” This misperception has resulted in “the misdirection of research, the misinterpretation of available evidence and the obstruction of a fuller and more accurate understanding of what psychiatric drugs do.”

Essentially all of the drugs currently used in psychiatry have been developed since the 1950s. While drugs were widely used before that time, they were seen as having crude effects, “usually acting as chemical forms of restraint.” Since that time, drug treatment has been seen as making psychiatry “truly scientific.” Part of this transformation was a radical change in theories of what drugs actually do. “Instead of being seen as substances that induced effects that were crude but useful, they came to be seen as specific treatments for specific illnesses. They became ‘cures.’”

As a consequence, Moncrieff called the current view of psychotropic drug action the “disease-centered model.”  It exists in two related forms. One suggests that drugs act on the underlying causes of a disease or condition. The other suggests that drugs act on the specific pathology responsible for producing the psychiatric symptoms.

This disease-centered model is assumed and rarely articulated. But its existence can be inferred from the way that psychiatric drugs are described and investigated. The names of drug classes themselves reflect this disease centered-model: antipsychotics; antidepressants; anti-anxiety medications. It begs the question of exactly what the biological state is that these drugs are supposed to correct. “The predominant psychiatric theory about this is colloquially referred to as the ‘chemical imbalance’ theory of psychiatric disorder.”

Moncrieff proposed an alternative model, that she called the “drug-centered model.” It suggests that the therapeutic value of a drug is derived from the particular quality of the abnormal brain state it produces. “Psychiatric drugs are psychoactive drugs which, by their neurophysiological effects alter ‘mental and emotional life and behaviour for the duration of the treatment.’” Here is a reproduction of a table Moncrieff used in The Myth of the Chemical Cure to show the differences between the two models:

Disease-centered model

Drug-centered model

Drugs help correct an abnormal brain state

Drugs create an abnormal brain state

Therapeutic effects of drugs derive from their effects on presumed disease pathology

Therapeutic effect derive from the impact of the drugs-induced state on behavioral and emotional problems

Drug effects may differ between patients and volunteers

Effects do not differ

Outcomes of drug research consist of effects of drugs on measures of the ‘disease’ and its manifestations or symptoms

Outcomes are the global state produced by drug ingestion and how this interacts with behaviors and experiences

Paradigm: insulin for diabetes

Paradigm: alcohol for social phobia/social anxiety

Along with their immediate effects, when psychiatric drugs are taken over a long period of time on a regular and frequent basis, they “induce physical adaptations to the presence of the drug.” These adaptations can be understood as the body’s defense against the effects of a foreign substance and have several consequences. First, they counteract the immediate effects of the drugs, so that larger doses are needed to achieve the same effects. In other words, tolerance to the drug occurs. A second adaptation occurs:

When the drug is stopped or reduced, especially if this is done suddenly, the bodily adaptations are suddenly unopposed by the presence of the drug. It is these unopposed adaptations that cause withdrawal symptoms and they may cause other problems such as precipitating an episode of psychiatric disorder.

If this is interpreted through the disease-centered model, the bodily reaction is interpreted as evidence of the supposed reactivation of an underlying psychiatric condition, rather than a withdrawal syndrome resulting from the decreased presence of the drug in the individual’s body. In opposition to this understanding, the drug-centered model of drug action suggests the effects of drugs used in psychiatry work essentially the same way that recreational drugs do.

In the case of recreational use of drugs, it is effects such as euphoria, stimulation, indifference, disinhibition, psychedelic experiences and some types of sedation that are sought after. These effects are valued as pleasant in themselves, and also as ways of blocking out and anasesthetising people against painful memories and current difficulties. Drugs used in psychiatry have a similar range of effects, and several psychiatric drugs are also drugs of misuse.

I have to confess that while I’ve spent my professional counseling career working with individuals struggling with drugs of abuse, the disease-centered model of drug action encompassed my worldview of the so-called mental disorders for too long. This was despite knowing on some level that what Joanna Moncrieff said was true.

There is a saying in Narcotics Anonymous (N.A.) that applies to the drug-centered model for psychiatric medications introduced here: “A drug is a drug is a drug.” We have lived too long with the disease-centered model of psychotropic drug action. A drug is a drug, regardless of whether it is alcohol, cocaine, Prozac or Seroquel. Psychotropic drugs do not correct abnormal brain states; they create them. You can watch YouTube videos of Joanna Moncrieff here (The Myth of the Chemical Cure: The Politics of Psychiatric Treatment) and here (De-mystifying psychiatric drugs). You can also go to her website for more information. She’s even made some of her published papers available.