Tag: The Myth of the Chemical Cure

08/11/20

Throwing Down the Gauntlet for ECT, Part 1

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Effective on December 26, 2018, the FDA issued a final order that required a premarket approval application for most uses of electroconvulsive therapy (ECT) devices. It also reclassified using ECT devices to treat catatonia or a severe major depression episode or bipolar disorder from Class III (higher risk) to Class II (moderate risk) with special conditions. This meant ECT manufacturers would have to submit information to the FDA demonstrating their ECT device complied with special controls that diminish known risks and provided an assurance of safety. These special controls were requirements about the technical limitations of the ECT device, about the labeling of potential adverse effects, about necessary practitioner training and a few aspects of clinical practice with the device. Carlos Pena, director of the Division of Neurological and Physical Medicine Devices for the FDA, said: “We remain committed to ensuring patients have access to reasonably safe and effective medical devices using the most current and scientifically robust information available.”

The reclassified uses for ECT devices into Class II are limited to the treatment of catatonia or a severe major depressive episode associated with major depressive disorder or bipolar disorder in patients age 13 years and older who are treatment-resistant or who require a rapid response treatment due to the severity of their psychiatric or medical condition. The safe use of ECT for treatment of these conditions has been well studied and is better understood than other uses. Therefore, sufficient information exists to establish special controls that mitigate known risks and provide a reasonable assurance of safety and effectiveness for these two uses of ECT devices. Manufacturers of ECT devices for the indications above will now need to submit information to the agency to demonstrate their devices are in compliance with these special controls.

A Premarket Approval (PMA) application is the scientific and regulatory review process the FDA uses to evaluate the safety and effectiveness of Class III medical devices. Class III devices support or sustain life, are of significant importance in preventing the impairment of human health, or they “present a potential, unreasonable risk of illness or injury.” PMA is based on the FDA determining there is sufficient, valid scientific evidence in the PMA application to assure the device is safe and effective for its intended use(s). The FDA determined that general and special controls alone were not sufficient to assure the safety and effectiveness of Class III devices.

For that reason, they required a PMA application from manufacturers to obtain marketing approval for their devices. A PMA application is required for all uses of an ECT device not specified as Class II, including disorders like schizoaffective disorder and bipolar manic states. This is because the FDA said it does not have sufficient information to establish special controls to provide a reasonable assurance of the safety and effectiveness of ECT devices for these indications.

In Psychiatric Times, Doctor Charles Kellner, who is the Chief of ECT Therapy ay New York Community Hospital, said the FDA’s final order was very good news in that it allowed for the ongoing availability of ECT devices in the US, but had “slightly less good news” in that what he referred to as “on label” indications was shorter than it had been in the past. With regard to the implications of the FDA order, he said most importantly moving depression into Class II ensures the majority of ECT patients will not have any change in their care. The way the order is written closely mirrors existing clinical practice. He estimated that major depression and catatonia account for 60% to 70% of current American ECT practice.

He emphasized that the FDA order does not regulate medical, clinical practice, meaning “practitioners are free to continue to prescribe ECT for any patient, regardless of diagnosis, whom they feel would benefit from the treatment.” Choosing to leave schizophrenia, schizoaffective disorder and mania in Class III was perplexing and disappointing to him, as he said schizophrenia was the leading indication globally for ECT and “the clinical and research evidence base support ECT as safe and effective for this illness.” He believed ECT devices will continue to be a small, but important part of psychiatric tools. From his contacts with other ECT practitioners around the country, he believed ECT use was increasing.

Dr. Kellner has spent most of his professional career in the study of ECT, especially with geriatric patients and can be understood as having a more positive view on the practice and future of ECT. But is his assessment accurate? Is the use of ECT increasing? Is the FDA final report good news and slightly less good news with regard to ECT or is it an overly optimistic view of both ECT and the FDA final rule?

Psychologist Phillip Hickey pointed out some inconsistencies in previous statements made by Dr. Kellner with regard to ECT that suggests his apparent optimism was at least partly playing to his perceived audience, other psychiatrists and medical doctors. In an editorial which he co-authored for the Journal of ECT, he said: “Despite its widespread acceptance in the medical community, ECT remains surrounded by ‘controversy.’” Yet in an earlier article for New Scientist, Kellner was quoted as saying “ECT ‘remains in the shadows’”, and described it as the second most controversial medical procedure after abortion. In the US and UK, only a tiny fraction of people whose depression doesn’t respond to medication are offered ECT.

Philip Hickey asked if only a tiny fraction of eligible patients were referred, “doesn’t this suggest that they [psychiatrists and other medical specialists] are, as a group less supportive of electric shocks” then Kellner claimed? He then cited a supporter of electric shock, George Kirov, a professor at Cardiff University who supervises ECT treatment in the city of Cardiff, Wales. Kirov acknowledged there are mixed feelings about ECT, even among psychiatrists. “If I speak to medical professionals outside of psychiatry, there is almost disbelief that we are using such an archaic practice.”

Joanna Moncrieff is a psychiatrist with reservations about the use of ECT in psychiatry. In her 2008 book, The Myth of the Chemical Cure, she acknowledged that ECT is still an accepted part of psychiatric clinical practice, but she thought its use was waning. She said it was the most controversial of current psychiatric treatments. The efficacy of ECT for depression in the short-term was still regarded as well-established, but she said it had no long-term effect. “In other words, a few weeks after the ECT has taken place, people are no better than they would have been if they had never had it.” She added:

The state produced by ECT offers several explanations for the apparent therapeutic effects of ECT. Firstly, the acute cognitive effects may temporarily override underlying emotional states and reduce people’s ability to express their emotions. The fact that the beneficial effects of ECT do not persist beyond the period of treatment would support this idea (Ross 2006).

Ross said the burden of proof is on ECT advocates to show that ECT can be prescribed ethically and rationally. He suggested a research study be conducted involving a randomized, prospective, double-blind, placebo-controlled design be done in which the placebo was sham ECT. But he wondered whether a true double blind was even possible in sham ECT research. “In the absence of such a study, whatever its outcome, the sham ECT literature supports the conclusions that: real ECT is no more effective than placebo, except during the period of time ECT is being administered; even that difference is modest.” He noted how the effectiveness of ECT was over-endorsed repeatedly in the psychiatric literature.

Moncrieff said other possible explanations for the apparent therapeutic benefit of ECT include the sedative and calming effects of ECT may produce improvement, particularly in people with agitated depression. The organic behavioral cycle produced by ECT, with its euphoria and disinhibition, can be mistaken as improvement. This is often misdiagnosed as mania, even in people with no history of manic depression. Lastly, ECT may work psychologically. In other words, patients may be able to break the double-blind methodology of the ECT control trials since the sham procedure cannot replicate the acute cognitive effects of ECT. Particularly if they have previously had ECT and believed ECT worked for them, they could be disappointed if they determined they had received the sham procedure. Conversely, they may do better if they received the real ECT treatment and were able to perceive it.

These explanations offered a more compelling explanation of the effects of ECT than the idea it was a specific treatment for major depression, according to Moncrieff. In addition, there is no currently accepted coherent theory of the efficacy of ECT or what it does to the brain that might help in depression:

(The jury is still out on ECT. Its use has survived much longer, despite widespread opposition from some psychiatric survivors and the fact that it is widely acknowledged that its effects are not persistent. Its effects can be explained by the acute cognitive impairment it causes, sometime amounting to a brain injury-like state that can be mistaken for recovery from depression.

Dr. Kellner may have an overly optimistic view for the future of ECT in the wake of the FDA final rule. I’d like to have some clear evidence one way or the other about whether ECT use is actually increasing. And I am not sure if the FDA final report is the “good news” he thinks it is. It appears to me the FDA has thrown down a gauntlet for medical device companies. They are to demonstrate their ECT devices are in compliance with special controls that diminish the known risks of ECT for Class II conditions.

And the companies are required to meet more stringent expectations, with sufficient and valid scientific evidence, that an ECT device does not “present a potential, unreasonable risk of illness or injury” if they want to claim their device as a treatment for Class III conditions. I hope the FDA remains committed to the stated standard of science described in their final rule on ECT. It will be interesting to see what the agency does with a recent publication in the Journal of Ethical and Human Psychology, “Electroconvulsive Therapy for Depression,” that raises the possibility that past support for ECT may be based on poor quality research. We will look at the claims of that study in Part 2 of this article.

06/23/20

The Complexities and Limitations of Buprenorphine, Part 1

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William White said he has for years tried to build bridges of communication across the polarized debates surrounding the use of medications in the treatment of addiction. He wrote “From Bias to Balance: Further Reflections on Addiction Treatment Medications” with a two-part goal in mind that I have borrowed and revised to frame my discussion here regarding the use of buprenorphine to treat opioid use disorder. The first part of White’s goal in “From Bias to Balance” was to help recovery advocates understand the positions of some who reject the use of medications as a pancea for opioid use disorders. The second part was to understand the complexities and limitations involved in the use of buprenorphine to treat opioid use disorders. For what it’s worth, I think I largely agree with White, even if I approach the issue more from the side of abstinence-based recovery.

Seeing medication-assisted treatment (MAT) as a polemic of medication haters and medication advocates muddies the waters by lumping different medications with radically different effects into the same category of MAT. According to SAMHSA in “Medication and Counseling Treatment,” the FDA has approved methadone, buprenorphine and naltrexone to treat opioid use disorder. Both methadone and buprenorphine are themselves scheduled substances by the DEA, meaning they each have a potential for misuse. This should be kept in mind when they are used to treat opioid use disorder, and be seen as a limitation of the respective medication. The other FDA-approved medications used for MAT, including those used to treat alcohol use disorder, are not scheduled substances and do not have the same limitation.

SAMHSA said a common misconception with MAT is that it substitutes one drug for another. According to SAMHSA, these medications are said to relieve the withdrawal symptoms and psychological cravings “that cause chemical imbalances” in the body. The phrase, “that cause chemical imbalances,” implies that the medications help correct an abnormal brain state, an assumption of what psychiatrist Jonanna Moncrieff called the disease-centered model of drug action in The Myth of the Chemical Cure. Buprenorphine and methadone do not balance or correct an abnormal brain state, in my opinion. They are as much exogenous, foreign bodily substances, as heroin or fentanyl are. I think Moncrieff’s alternative model, the drug-centered one, more appropriately captures both the effects of the originally misused drug and the medication used to treat it.

Joanna Moncrieff developed her drug-centered and disease-centered models of drug action to describe how psychiatric medications work, but they also apply to all psychoactive substances, all mind-altering and mood-changing chemicals. The disease-centered model of drug action seems to underlie the uncritical advocacy of medications for opioid use disorders. “Psychiatric drugs [including methadone and buprenorphine] are psychoactive drugs which, by their neurophysiological effects alter ‘mental and emotional life and behaviour for the duration of the treatment.’” Along with their immediate  and sometime euphoric effects, when psychoactive medications are taken over a long period of time on a regular basis, they “induce physical adaptations to the presence of the drug.” These adaptations have several consequences, including the following.

When a psychoactive medication is used on a regular, frequent basis, the body attempts to counteract the effects of the drug, which it sees as an invading, foreign substance. In time, a kind of homeostasis is reached between the effects of the psychoactive medication and the body’s adaptations to it. This often leads to the development of tolerance, meaning that larger doses of a medication are needed to achieve the original psychoactive effects. When the medication is stopped or reduced too rapidly, the body’s adaptations overpower the weakened or absent medication effect and symptoms of withdrawal or discontinuation become evident.

When this process is viewed through the lens of a disease-centered perspective, the body’s reaction is interpreted as evidence of the reemergence of the underlying condition which the medication had “balanced.” In this case, opioid use disorder. And the recommended treatment is then a continuation of the psychoactive medication to maintain that balance, perhaps indefinitely. Instead of a disease-centered view of restoring chemical balance, I think opioid medications like methadone and buprenorphine relieve withdrawal symptoms and psychological cravings by creating their own abnormal brain state. This view is consistent with Moncrieff’s drug-centered model of drug action.

See “A Drug Is a Drug Is a Drug” or search this website for “the disease-centered model” for more on this topic. Also see “Models of drug action” on Jonna Moncrieff’s blog and “Rethinking Models of Psychotropic Drug Action.” Nevertheless, as William White said, medications can play a valuable role in addiction treatment:

Medications can play a valuable role in harm reduction, recovery initiation, and recovery maintenance for populations for whom they are indicated and acceptable, but we do a disservice to those populations, their families, and their communities if we portray medication alone as a panacea for the cure of all opioid addiction and fail to carefully communicate both the potential value and the limitations of medications. Issues like the above [see “From Bias to Balance”] need to be part of our nuanced discussions with those we serve. We similarly do a disservice if we let anti-medication polemics go unchecked within our local and national conversations.

Medications are best viewed as an integral component of the recovery support menu rather than being THE menu, and their value will depend as much on the quality of the milieus in which they are delivered as any innate healing properties that they possess. If the effectiveness of medication-assisted treatment (MAT) programs is compromised by low retention rates, low rates of post-med. recovery support services, and high rates of post-medication addiction recurrence, as this review suggests, then why are we as recovery advocates not collaborating with MAT patients, their families, and MAT clinicians and program administrators to change these conditions?

People seeking recovery from opioid use disorders and their families are in desperate need of science-grounded, experience-informed, and balanced information on treatment and recovery support options—information free from the taint of ideological, institutional, or financial self-interest.

Consistent with a drug-centered model of medication action, the potential risks and benefits of buprenorphine as a MAT need to be objectively and scientifically assessed. One of the complexities and a limitation of buprenorphine-based MAT is the fact that it is a Schedule III controlled substance, with a moderate to low potential for physical and psychological dependence. There is also a higher risk of harm, including overdose and death, when buprenorphine is combined with benzodiazepines or other sedatives like alcohol. Because of this danger, information was added to the Boxed Warning on the Medication Guides by the FDA for buprenorphine products on the risks of slowed or difficult breathing and death. Even before it was approved as a MAT, in the US, buprenorphine was known to have problems with diversion and misuse.

While the risks of misuse are lower for buprenorphine than for most other opioids in the US, this is not true in many European and Asian countries. Illicit buprenorphine use has been reported in Sweden, Scotland, Norway, Ireland and Spain. In Finland buprenorphine is the most widely abused opioid. In 2001 Finland had a sharp increase in the misuse of buprenorphine that coincided with a decrease in the availability of heroin. Seventy-three percent of a sample of participants in a Finnish syringe exchange program reported buprenorphine was their most frequently abused injection drug. Participants also used it as a self-treatment for withdrawal.

In “From Bias to Balance,” William White noted the standard practice with medications is to define the precise condition a medication is best suited to treat, and then identify patients who should not be prescribed the medication because of potential harm, meaning the risks outweigh the potential benefits for them. Yet after more than a century of attempts to treat opioid addiction with medications, there is no clinically defined protocol for who is most likely to benefit from pharmacotherapy. Additionally, “the question of potential degree of help or harm of medications in the treatment of addiction is unanswerable without also asking, “‘For whom?’ ‘For what purpose?’, ‘For how long?’, and ‘At what cost?’.”

White said the addiction treatment field has yet to reach consensus on what is the optimal duration of medical support in treatment of opioid use disorder. I think this impasse partly reflects the unacknowledged presumption of Moncrieff’s disease-centered model of drug action among medication advocates. The disease-centered model is itself a product of what is called the medical model, which sees psychopathology as the result of biology; a physical/organic problem in brain structures, neurotransmitters, etc. The over reliance on the medical model perspective (and the disease-centered model of drug action) in addiction treatment leads to an imperfect conception of substance use disorder and a distorted understanding of the risks and benefits of buprenorphine when it used to treat opioid use disorder.

Self-consciously taking a drug-centered model of drug action with buprenorphine and rejecting the medical model perspective of substance use disorders is necessary to truly reach a consensus on the potential degree of help or harm of buprenorphine in the treatment of opioid addiction. Consider what Joanna Moncrieff said in The Myth of the Chemical Cure when contrasting her two models of drug action to the use of buprenorphine in MAT:

The disease-centred model suggests that the important or ‘therapeutic’ effects of drugs are achieved by their effects on a particular disease process. By acting on the mechanisms of the disease, drugs move the human organism from an abnormal physiological state towards a more normal one. In contrast, the drug-centred model suggests that drugs themselves create abnormal bodily states. In the case of drugs that act on the brain or the nervous system, these states involve an alteration in subjective experience or consciousness. Psychiatric drugs [including buprenorphine, I would add] are psychoactive drugs which, by their neurophysiological effects alter ‘mental and emotional life and behavior for the duration of the treatment’ (Cohen & Jacobs 2007). When we consider drugs that are taken recreationally we have no trouble recognizing this fact and we refer to the altered mental state drugs produce as ‘intoxication’. But there is no fundamental distinction between drugs used for psychiatric purposes and other psychoactive drugs. They all act on the nervous system to produce a state of altered consciousness, a state that is distinct from the normal undrugged state.

The impasse between so-called medication haters and medication advocates is philosophical, not scientific. Beginning with a drug-centered model of buprenorphine can help us move forward in correctly addressing questions on the potential degree of help or harm buprenorphine brings to the treatment of addiction. We can more clearly discuss the complexity and limitations of using buprenorphine, an opioid medication, to treat opioid use disorder when that treatment is viewed through a drug-centered model of medication action.

02/25/20

Rethinking and Transforming Psychiatry

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“We believe that a fundamental rethinking of psychiatric knowledge creation and training is in order.” This statement was made in a commentary published in the New England Medical Journal, “Medicine and the Mind—The Consequences of Psychiatry’s Identity Crisis.” The authors are two prominent Harvard researchers in psychiatry, Caleb Gardner and Arthur Kleinman, so their words cannot be dismissed as ‘anti-psychiatry.’ They went on to say biologic psychiatry has so far failed to produce a comprehensive theoretical model for any major psychiatric disorder. However, they think it would be “too great a loss,” to diminish its role drastically as suggested by Anne Harrington. Rather than contracting to an exclusive focus on biologic structure, “the field needs to expand if we are to meet the needs of real people.”

I have mixed feelings about their proposal. Their critique of biological psychiatry, the acknowledgment of over prescribing psychiatric medication, the abandonment of its social, interpersonal, and psychodynamic foundations are concerns I share. But they balked at Anne Harrington’s proposal in Mind Fixers to limit its scope to severe, mostly psychotic disorders. She said there is hardly any knowledgeable person who believes the so-called biological revolution of the 1980s made good on its therapeutic and scientific promises. “It is now increasingly clear to the general public that it overreached, overpromised, overdiagnosed, overmedicated, and compromised its principles.” If psychiatry needed to be rebuilt, as the authors said, won’t there have to be some dismantling first? Otherwise, there is a danger of building on an unstable, unreliable foundation.

Harrington pointed to how in 2013, just before the publication of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Thomas Insel, who was then the director of NIMH, said the agency was re-orienting its research away from DSM categories; that is was critical to realize that “we cannot succeed if we use DSM categories as the ‘gold standard’” for diagnosis. He said it was like using the nature of chest pain or the quality of a fever to create a diagnostic system. Harrington said, “Put another way, there seemed to be little if any sound biology undergirding the psychiatric enterprise.”

In Psychology Today, Jonathan Shedler wrote, “A Psychiatric Diagnosis Is Not a Disease.” He said there was a circular logic to psychiatric diagnosis. “How do we know a patient has depression? Because they have the symptoms. Why are they having symptoms? Because they have depression.” He elaborated that psychiatric diagnoses were categorically different from medical diagnoses like atherosclerosis, myocarditis, or pneumonia, because they are descriptive rather than explanatory. “Medical diagnoses point to etiology—underlying biological causes.”

In an addendum, Shedler said he appreciated the lively discussion his article inspired. He was surprised by some of the comments, from individuals he assumed to be psychiatrists, who had impugned his credentials to discuss psychiatric diagnosis. But he took comfort in knowing that Allen Frances, MD, Chair of the DSM-IV Task Force, had the same view. Frances also said mental disorders were not diseases, but constructs. They were descriptive, rather than explanatory.

There was a study published in Psychiatry Research, “Heterogeneity in Psychiatric Diagnostic Classification,” that examined the heterogeneous nature of categories within the DSM-5, and its consequences for clinicians, clients and the diagnostic model itself. Heterogeneity was found in specific diagnostic criteria, including symptom comparators, duration of difficulties, indicators of severity, and the perspective used to assess difficulties. Each of the three researchers called for dismantling, not expanding DSM diagnosis.

The lead researcher of the study, Kate Allsopp, said for Medical Express: “Although diagnostic labels create the illusion of an explanation they are scientifically meaningless and can create stigma and prejudice.” Peter Kinderman, another author, said: “This study provides yet more evidence that the biomedical diagnostic approach in psychiatry is not fit for purpose.” He added the diagnostic system wrongly assumed that all distress resulted from disorder. John Read, who was the third author, said: “Perhaps it is time we stopped pretending that medical-sounding labels contribute anything to our understanding of the complex causes of human distress or of what kind of help we need when distressed.”

Psychiatric Times published an interview with Allen Frances for Conversations in Critical Psychiatry. Although he thought psychiatry was among the noblest of professions, “I fear that too many psychiatrists are now reduced to pill pushing, with far too little time to really know their patients well and to apply the rounded biopsychosocial model that is absolutely essential to good care.” He despaired that diagnostic inflation resulted in a too loose of a diagnostic system. “Diagnoses should be written in pencil, and under-diagnosis is almost always safer and more accurate than over-diagnosis.” With regard to epidemiological studies that tend to exaggerate rates of mental disorders, Frances said:

Never believe the extremely high rates of mental disorders routinely reported by epidemiological studies in psychiatry—usually labelling about 25% of the general population as mentally ill in the past year, about 50% lifetime. This entire literature has a systematic, but unacknowledged, methodological bias that inherently results in over-reporting. Because epidemiology requires such huge samples—in the tens of thousands—it is prohibitively expensive to conduct clinical interviews. Instead phone surveys are done by non-clinicians following a highly structured format that allows no clinical judgment whether the symptoms reported cause sufficient clinically significant distress and impairment to qualify as a mental disorder. Since there is no sharp boundary between normal distress and mental disorder, not assessing for clinical significance includes among those labelled mentally ill many who are merely distressed. The rates reported in studies are really only upper limits, not accurate approximations of true rates. They should be, but never are, reported as such.

His final word on DSM was: “DSM should be seen only as a tool helpful in guiding clinical judgment, not as a replacement for it.”

Returning to “Medicine and the Mind” by Gardner and Kleinman, psychiatrist Sandy Steingard said she shared their wish that research funding would be allocated to fields other than basic biologic research. But she was surprised they appeared to support buttressing psychiatry’s hold as leaders in research and program development. “I need some convincing that the problems we agree exist will be best addressed within my profession. In recent years, I have been most impressed by approaches to mental distress that emanate from outside of psychiatry.”

Finally, there was an article published in Public Understanding of Science that aimed to analyze the ‘critical reception’ of the DSM-5—how it has been received, discussed and criticized by different categories of people: “The Critical Reception of the DSM-5.” They noted two major themes surrounding the critical reception of the DSM-5, the pseudo-scientific nature of the manual and its normalizing power. Mental health professionals, especially psychiatrists, were more invested in the debate on the scientific nature of the DSM-5. There was a more eclectic variety of audiences in the debate over the normalizing power of the manual.

In the first debate (the scientific nature of the DSM), we found opposing argumentative positions regarding whether or not the manual is a scientific tool and questioning the type of science to which the manual adheres. In the second debate (the normalising power of the DSM), opinions were also polarised: while some argued that the manual was potentially socially harmful, some pointed out its lack of inherent agency and others mentioned its potential benefits. Although these debates have been noted in previous studies (Demazeux, 2015; Ecks, 2016), our research aims to deepen the understanding of such discussions.

They concluded the DSM was not simply a scientific manual. Rather, it is “a social laboratory where political, sociological, ethical and psychological issues are discussed and confronted.” In order to critically analyze the DSM, the authors said it was important to consider the claims that challenge the APA’s narrative of the DSM, namely its scientific and democratic nature. They said a range of arguments interacted and overlapped “in differing and opposing ways.” This was said to nuance the idea often presented academic publications that critiques of the DSM were mostly fixed, repeating the same themes and antagonistic positions.

The above issues were not being discussed in fringe, antipsychiatry forums. Rather, they appeared in well-received, medical and psychological arenas: The New England Medical Journal, Psychology Today, Psychiatry Research, Medical Express, Psychiatric Times, the National Institute of Mental Health. The people addressing them: Allen Frances, Thomas Insel, Caleb Gardner, Arthur Kleinman and others are or were key individuals within the mental health, psychiatric, diagnostic fields. The time is coming where just discussing the issues and concerns will not be enough; change will be necessary.

Psychiatry and diagnosis need to be reined in. They have extended their “reach” too far as it is, and scaling back is a necessary and essential step before any future recasting of the role of psychiatric treatment for mental “disorders.” Anne Harrington’s suggestion to limit its scope to severe, mostly psychotic disorders is a good first step. Dr. Joanna Moncrieff, a psychiatrist, seems to share this view. In “Rethinking Modals of Psychotropic Drug Action,” and “The Psychoactive Effects of Psychiatric Medication,”  she proposed a “drug centered model” of drug action, rather than the existing “disease centered model,” whose core assumption is that psychotropic drugs help correct “a biochemical abnormality that represents a biological substrate of a specific disease process.”

In The Myth of the Chemical Cure, Moncrieff acknowledged abandoning the disease-centered model would challenge “some of the most fundamental principles of modern psychiatry.” Yet she said it would also open the way “to a more honest practice” that requires its own specialist knowledge, and implements a more democratic treatment process:

Adopting a drug-centred model of drug action would require psychiatrists to become more informed about the effects of different psychoactive drugs, and become attuned to evaluating the subjective experiences of their patients in a more equal and reciprocal relationship. Where their function was to participate in mechanisms of social control this would be openly acknowledged and rigidly controlled rather than veiled, as currently, under the cloak of medicine.

In “The Psychoactive Effects of Psychiatric Medication,” she pointed out how re-orienting drug therapy towards a drug-centered model raised some questions about the validity and relevance of diagnostic systems like the DSM-5. The idea that psychiatric drugs exert “a disease- or disorder-specific action” has been one of the principal justifications for modern psychiatric classification. Using psychiatric drugs explicitly for their psychoactive effects would require a different understanding of the nature of psychiatric problems. It would break the link between diagnoses and treatment, “and enable a frank discussion about the purpose and ethics of the already frequent ‘off-label’ use of prescribed psychoactive medications, such as their use for behavioral control in children and the elderly.”

Gardner and Kleinman were not advocating going this far, but I think psychiatry needs a transformation. Long live the transformation!

07/12/16

Common Sense with Lithium

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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!

11/5/14

A Drug is a Drug is a Drug

lightwise / 123RF Stock Photo
lightwise / 123RF Stock Photo

“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.