10/3/24

The Medication Merry-Go-Round with Depression

Photo by michaelangelo ramos on Unsplash

There seems to be a paradigm shift brewing for how we explain depression. “Beyond the serotonin deficit hypothesis,” an article that appeared in Molecular Psychiatry, noted how the serotonin deficit hypothesis of depression has persisted among clinicians and the general public alike “despite insufficient supporting evidence.” The next month the journal Psychopathology published a study, “A Descriptive Diagnosis or a Causal Explanation?” that concluded leading professional medical and psychiatric organizations commonly confound a descriptive diagnostic label for depression with a causal explanation. Then there was a third study that explored whether the DSM adequately identified DSM disorders when someone was decreasing, switching, or discontinuing SSRIs/SNRIs following their long-term use.

The End of the Serotonin Theory of Depression

In 2022 an article in Molecular Psychiatry, “The serotonin theory of depression: a systematic umbrella review of the evidence,” concluded the serotonin theory has not produced convincing evidence of a biochemical basis for depression. The researchers suggested it was time to acknowledge that the serotonin theory of depression was not empirically substantiated. The flurry of criticism the article generated didn’t seem to stifle its message. “Beyond the serotonin deficit hypothesis” said in order to combat the eroding public trust in science and medicine (and also combat the rising mental health crisis), “researchers and clinicians must to be able to communicate to patients and the [general] public an updated framework of major depressive disorder (MDD).” These authors suggested that framework should be:

(1) accessible to a general audience, (2) [it should] accurately integrate current evidence about the efficacy of conventional serotonergic antidepressants with broader and deeper understandings of pathophysiology and treatment, and (3) [be] capable of accommodating new evidence.

They discussed how MDD could be understood as inflexibility in cognitive and emotional brain circuits that involved a persistent negative bias. Secondly, they reviewed how effective treatments for MDD enhanced mechanisms of neuroplasticity in ways that facilitated adaptive and emotional processing. Lastly, they considered how researchers, clinicians and other professional could present this framework when discussing MDD with patients or the general public. They also suggested language and metaphors they thought could be useful for effective communication about MDD. For a further discussion of “The serotonin theory of depression,” see: “Paradigm Shift Needed with Depression.”

Is MDD a Description or a Causal Explanation?

In “A Descriptive Diagnosis or a Causal Explanation?” two Finnish researchers observed: “Psychiatric diagnoses are descriptive in nature, but the lay public commonly misconceives them as causal explanations.” Kajanoja and Valtonen said it was not known to what extent this form of diagnostic circular reasoning—diagnoses being discussed as if they describe the causes of symptoms—was mistakenly reinforced by the health authorities themselves. They investigated the prevalence of misleading causal descriptions of depression in the information on the websites of authoritative mental health organizations. Most websites used language “that inaccurately described depression as a causal explanation to depressive symptoms.”

Most psychiatric diagnoses are descriptive: They describe states of mental distress and dysfunction but do not in themselves contain causal explanations. Nonetheless, diagnoses in psychiatry are commonly talked about as if they are concrete entities that explain the symptoms they describe. In this study, we examined whether health organizations themselves contribute to this logical fallacy. We searched for popular websites managed by leading mental health organizations, and evaluated whether they discussed the diagnosis of depression accurately as a description, or inaccurately as a cause for depressive symptoms. We found that the majority of websites presented depression as a cause, instead of a description of symptoms. We discuss the potential harmful consequences of inaccurately presenting descriptive psychiatric diagnoses as causes.

In “Depression Diagnoses Debunked,” SciTechDaily said Kajanoja and Valtonen selected the websites of English-language organizations that seemed to be the most influential ones providing information on depression. These organizations included the World Health Organisation (WHO), the American Psychiatric Association (APA), National Health Service (NHS) in the UK, Harvard and Johns Hopkins Universities, among others. They found most of the organizations portrayed depression as a disorder that caused symptoms and/or explained what caused the symptoms. None of the organizations presented the diagnosis of MDD as a pure description of symptoms. They said:

Presenting depression as a uniform disorder that causes depressive symptoms is circular reasoning that blurs our understanding of the nature of mental health problems and makes it harder for people to understand their distress. . . People seem to have a tendency to think that a diagnosis is an explanation even when it is not. It is important for professionals not to reinforce this misconception with their communication, and instead help people to understand their condition.

Misdiagnosing Antidepressant Withdrawal

A third study by Cosci, Chouinard and Chouinard published in Psychotherapy and Psychosomatics explored whether the DSM alone was adequate to identify psychiatric disorders when an individual was switching, decreasing or discontinuing a SSRI/SNRI. The researchers found that withdrawal/discontinuation symptoms were mis-formulated (misdiagnosed) as DSM-5 psychiatric disorders like a current panic disorder or recurrent major depressive disorder. They noted how existing diagnostic methods with the DSM do not take withdrawal/discontinuation phenomenon into account. The researchers used a new nosographic system, the Diagnostic Clinical Interview for Drug Withdrawal 1-New Symptoms of Serotonin Reuptake Inhibitors or Serotonin-Norephinephrine Reuptake Inhibitors (DID-W1), and found that: “In 58 cases (77.3%), the DSM-5 diagnosis of current mental disorder was not confirmed when the DID-W1 diagnosis of current withdrawal syndrome was established.”

Reviewing the Cosci, Chouinard and Chouinard article for Mad in America, “Antidepressant Withdrawal Commonly Misdiagnosed as ‘Mental Illness’,” Peter Simons said the researchers thought the fact that the DSM does not include criteria for withdrawal symptoms was a barrier to the accurate diagnosis and treatment of depression. “While the DSM asks clinicians to differentiate ‘mental disorders’ from drug-induced symptoms, it does not include drug withdrawal symptoms—from either recreational or prescribed drugs.” Therefore, Cosci, Chouinard and Chouinard suggested the DID-W1 be used to detect withdrawal induced by SSRI/SNRI discontinuation, decrease or switching all psychiatric medications. Limitations of the study included the small sample size, and that study participants were volunteers who were already seeking help for withdrawal reactions.

It seems that when switching, decreasing or discontinuing antidepressants (or antipsychotics) leads to circular reasoning—withdrawal symptoms that can be misdiagnosed as an emerging anxiety disorder, some other psychiatric disorder, or seen as the re-emergence of major depression. Without a tool like the DID-W1, what can a person do to better understand their problems and get off the medication merry-go-round for depression?

The Model of Drug Action May Be the Answer

Joanna Moncrieff, one of the researchers who wrote “The serotonin theory of depression: a systematic umbrella review of the evidence”, has promoted what she calls “the drug-centered model of drug action.” She has written about it multiple times and her discussion can be found in The Myth of the Chemical Cure, on her blog in “Models of Drug Action,” and in “Research on a ‘drug-centred’ approach to psychiatric drug treatment” published in the peer-reviewed journal, Epidemiology and Psychiatric Sciences. In “Models of Drug Action,” she said she formulated two different models of drug action, the disease-centered model, and the drug-centered model. Also see “A Drug is a Drug is a Drug.”

The disease-centered model suggests that psychiatric drugs can reverse, or partially reverse, “the disease or abnormality that gives rise to the symptoms of a particular psychiatric disorder.” This model is borrowed from general medicine and describes drugs through the prism of disease or the collective pattern of symptoms the drugs are thought to treat. The important effects of the drugs—like with serotonin reuptake inhibitors— “are the ones they exert on the disease process.” All other effects are considered to be ‘side effects.’ And the therapeutic effects are believed to only be evident in people with the ‘disease.’

The drug-centered model suggests that psychiatric drugs induce an abnormal or altered state, but do not correct it. Psychiatric drugs like antidepressants are psychoactive substances like alcohol or heroin, and they modify the way the brain functions, producing changes in thinking, feeling and behavior. They exert their effects on the individual regardless of whether or not they have a mental condition (a drug is a drug). The drug-centered model suggests that some drugs may be useful therapeutically in some situations, but not by normalizing brain function. “They do it by creating an abnormal or altered brain state that suppresses or replaces the manifestations of mental and behavioural problems.” See also “Never Enough and No Free Lunch” and “Never Enough and Adaptation.”

See the following table for a comparison of the two models, taken from “Research on a ‘drug-centered’ approach to psychiatric drug treatment.”

When modern psychiatric drugs were introduced in the 1950s, they were understood according to a drug-centred model. Antipsychotics, for example, which were then known as ‘major tranquilisers,’ were regarded as a special sort of sedative. They were thought to have properties that made them uniquely useful in situations like an acute psychotic episode, because they could slow up thought and dampen emotion without simply inducing sleep, but they were not regarded as a disease-targeting treatment. By the 1970s, however, this view was eclipsed and the disease-centred model of drug action became dominant. Accordingly psychiatric drugs were regarded as specific treatments that worked by targeting an underlying disease or abnormality. The change is demonstrated most clearly in the way drugs have come to be named and classified. Prior to the 1950s drugs were classified according to the nature of the psychoactive effects they produce. Existing drugs were crudely classified as having either sedative or stimulant effects on the nervous system. After the 1950s, however, drugs came to be named and classified according to the disease or disorder they are thought to treat; antidepressants, antipsychotics and anxiolytics, for example.

The ascendance of the disease-centred model of drug action did not occur because of overwhelming evidence of the superiority and truth of the disease-centred model. There was not then, and is not now, convincing evidence that any class of psychiatric drugs has a disease centred or disease-specific action. There was not even any real debate about alternative theories of drug action. The disease centred model just took over and the drug-centred view simply faded away. People forgot there had ever been another way of understanding how psychiatric drugs might work.

In summary, we should set aside the serotonin theory of depression because it has not produced convincing evidence of a biochemical basis for depression. Psychiatric diagnosis appears to be circular reasoning that describes states of mental distress, but does not provide a causal explanation of that distress. The withdrawal symptoms when tapering, discontinuing or changing antidepressant medications leads to a misdiagnosis of recurrent major depression or another psychiatric disorder. We need to return to a drug-centered model of drug action to get off of the medication merry-go-round.

It seems we are beginning to pay attention to a question asked by psychiatrist Peter Breggin 25 years ago in Your Drug May Be Your Problem: “Do we know what we are doing to our brains and minds when we take psychiatric drugs?” Doctor Breggin said: “We simply do not understand the overall impact of drugs on the brain.”

Consider this extraordinary reality. The human brain has more individual cells (neurons) than there are stars in the sky. Billions! And each neuron may have 10,000 or more connections (synapses) to other brain cells, creating a network with trillions of interconnections. In fact, the brain is considered to be the most complex organ in the entire universe. With its billions of neurons and trillions of synapses, it is more complex than the entire physical universe of planets, stars, and galaxies . . .

Those trillions of interconnections between brain cells … are mediated by hundreds of chemical messengers (neurotransmitters), as well as hormones, proteins, tiny ions, such as sodium and potassium, and other substances. We have limited knowledge about how a few of these chemical messengers work but little or no idea as to how they combine to produce brain function.

06/30/20

The Complexities and Limitations of Buprenorphine, Part 2

William White wrote “From Bias to Balance: Further Reflections on Addiction Treatment Medications” in an attempt to open a dialogue between the polarized sides of using opioid medications like buprenorphine to treat opioid addiction. In Part one of this article I expressed my belief that the impasse between the two sides is largely for philosophical, not scientific reasons. Medication advocates presume what Joanna Moncrieff calls a disease-centered model of drug action that leads to the belief and portrayal of certain medications as a panacea for opioid use disorders, something that the so-called medication haters soundly reject. I suggested that beginning instead with what Moncrieff calls a drug-centered model would allow for a more productive dialogue on the complexity and limitations of using buprenorphine to treat opioid use disorder.

In “Rethinking Models of Psychotropic Drug Action,” Joanna Moncreiff described the distinctions between two different types of drug action, the disease-centered model and the drug-centered model. She added that theoretical assumptions about how psychotropic drugs work are rarely discussed explicitly. The disease-centered model underlies orthodox psychopharmacology. It assumes that a psychotropic drug like buprenorphine helps correct a biochemical abnormality. In other words, medications are understood to work by acting on a disease process.

This notion, sometimes called the ‘chemical imbalance’ theory, is the implied view of SAMHSA, which says MAT medications (like buprenorphine) “operate to normalize brain chemistry.” But in a ‘drug-centered model’ the distinctive physiological, behavioral and subjective effects of drugs are used to define drug action. “The therapeutic value of a drug stems from the usefulness of these effects in clinical situations.”

In this approach, drugs are seen to induce characteristic physiological and subjective states that may, or may not, be experienced as useful in certain social and interpersonal situations, including clinical situations. Unlike the disease-centred model that assumes that drugs move an abnormal physiological state towards a more normal one, the drug-centred model suggests that drugs create their own characteristic abnormal states or alterations of normal states. It is these states or effects that need to be described and understood, and the potential therapeutic value of a drug is deduced from this understanding. It is therefore implied that diagnosed patients and normal volunteers’ basic physiological responses to drugs will differ only in so far as a degree of individual variation in drug response (including variation in arousal, set, biological sensitivity) always exists.

Consistent with what Moncrieff said here regarding the drug-centered model, in “From Bias to Balance,” William White said the potential risks and benefits of medication support when treating opioid addiction are not uniform. He thought recovery advocates needed to have a general knowledge of the evolving science and the clinical experience with regard to the overall benefits and risks associated when medications like buprenorphine are used in medication-assisted treatment—what the side effects are, when and for whom it is indicated and contraindicated. “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 that despite knowing that people recover from opioid addiction with and without medication support, the addiction treatment field still has not clinically defined who would benefit most from pharmacotherapy and for whom it would be contraindicated. He thought answering that question would be a major step forward.

The potential differences between those who achieve stable recovery (five years plus of opioid abstinence) from opioid use disorder through pharmacotherapy and those who achieve stable recovery without medication support are unclear. Nearly 40% of Narcotics Anonymous (NA) members report regular use of narcotics and an average of 8.2 years of continuous recovery. This would seem to challenge the bleak prospects of recovery from opioid addiction without medication support that dominates the professional literature and popular media. “Yet such recoveries from opioid use disorders within NA remain a rare focus of scientific study.”

There is also no consensus on the optimal duration of medication-assisted support in the treatment of opioid use disorder. SAMHSA said the length of time should be tailored to each patient and could be indefinite. In SAMHSA’s TIP 63, the section “Duration of Buprenorphine Treatment,” stated there was no known duration of buprenorphine therapy where patients could be certain they would not return to illicit opioid use. “Patients should take buprenorphine as long as they benefit from it and wish to continue.” ASAM, the American Society of Addiction Medicine, echoed SAMHSA’s indefiniteness, giving the following advice in their “National Practice Guideline” for the length of treatment with buprenorphine when treating opioid use.

There is no recommended time limit for treatment with buprenorphine. Buprenorphine taper and discontinuation is a slow process and close monitoring is recommended. Buprenorphine tapering is generally accomplished over several months. Patients and clinicians should not take the decision to terminate treatment with buprenorphine lightly.

Consistent with this reluctance to define or investigate a time limit for treatment with buprenorphine, William White said there has been inadequate attention to the process of tapering when clients choose to maintain their recovery without medication. The statistics reported in the research literature on those who attempt buprenorphine treatment are not promising. Meinhofer et al reported that over one-half (55%) of individuals discontinued buprenorphine within about six months and 13% experienced at least one adverse opioid-related event within 360 days of starting with buprenorphine. Hser et al reported that only 46% of buprenorphine participants completed 24 weeks of treatment; 24.8% dropped out within the first 30 days.

White stated the reality is that many patients who begin MAT for opioid addiction stop taking the medications within a matter of months. He cited a study of adolescents and young adults, “Receipt of Timely Addiction Treatment,” that found the median retention of those who did use buprenorphine was less than six months. Could it be that the intent to limit the risk of overdose mortality by leaving the time limit for MAT with buprenorphine open-ended has led to a perceived “Hotel California” effect in buprenorphine treatment? You can check in anytime you want, but you’ll find you can never leave. Open-ended treatment protocols like the SAMHSA and ASAM recommendations for buprenorphine leads abstinence-based recovery advocates and some addicts to conclude the goal is to keep patients “parked” on medication forever.

One factor influencing the open-ended recommendations for MAT is the high risk of overdose mortality when an opioid addict resumes active use. In the four weeks following the cessation of medication maintenance, death rates as high as four times that of patients who remain in treatment have been reported, due to the lost tolerance from their abstinence. This parallels the risk of overdose mortality after the release from a prison, hospital or inpatient/residential addiction treatment program.

One of White’s suggested action steps was to expand supports available for patients during and after medication tapering. According to ASAM, factors associated with the successful termination of treatment with buprenorphine are not well described, but may include the following:

Employment, engagement in mutual help programs, or involvement in other meaningful activities.
Sustained abstinence from opioid and other drugs during treatment.
Positive changes in the psychosocial environment.
Evidence of additional psychosocial supports.
Persistent engagement in treatment for ongoing monitoring past the point of medication discontinuation. Patients who relapse after treatment has been terminated should be returned to treatment with buprenorphine.

White said long-term follow-up studies of people with opioid use disorders find that between a third and half of those who achieve stable recovery have far less problem severity and complexity and have great recovery capital (e.g., education, employment, family and social support).

The overwhelming majority of addiction medication providers assert the value of psychosocial interventions as a critical component of addiction treatment, but little more than a third report that their organizations and local communities have the resources to provide such interventions for patients using medication to support recovery from an opioid disorder.

A final complexity and limitation with buprenorphine as an opioid medication is that buprenorphine is itself an opioid. Given Moncrieff’s drug-centered model of medication action, this reality needs to be acknowledged by treatment professionals and addressed when evaluating the overall benefits and risks of buprenorphine. The potential degree of help or harm it may incur should also be discussed honestly and openly with the individual. One of the likely effects an individual should expect when tapering off of buprenorphine is the emergence of a withdrawal or discontinuation syndrome.

In Part 1 of this article, I discussed how according to the drug-centered model, when psychoactive medications like buprenorphine are taken over a long period of time, they “induce physical adaptations to the presence of the drug.” The body attempts to counteract the effects of the drug, which it sees as a foreign, exogenous substance. In time, a kind of homeostasis is reached between the effects of the medication and the body’s adaptations to it. When the medication is stopped, the body’s adaptations overpower the now weakened medication effect and symptoms of withdrawal or discontinuation are evident. I’d suggest this is likely with years of medication maintenance and even after a slow, gradual taper.

The taper event should be addressed clinically as a relapse trigger and the resulting withdrawal symptoms understood simply as that; and not as a reemergence of the ‘disease state’ that will lead back to active use if buprenorphine maintenance is not resumed. I think this discontinuation or withdrawal is best understood as the delayed manifestation of post-acute withdrawal (PAW) symptoms. The original use of an opioid recreationally was supplanted by an opioid (buprenorphine) used as a MAT and the original emergence of PAW symptoms was muted or never truly occurred.

I’ve added the thinking of Terrance Gorski on recovery and relapse to the discussion here. See “Preventing the Relapse Process,” Part 1 and Part 2 for a discussion of relapse. See “Managing Your PAWS” and “Recognizing Your PAWS” for a discussion of post-acute withdrawal. Also see the Gorski-CENAPS Corporation for his books and workbooks.

I think there can be productive dialogue between the two opposing views of medication-assisted treatment. A necessary first step is to see buprenorphine and opioid use disorder through the lens of the drug-centered model of medication action. Then there can be discussions of the complexities and limitations of treating opioid use disorder with an opioid. Research won’t have to ignore that elephant in the methodology. And then we can begin to do the truly important work of answering the questions—for whom, for what purpose, for how long and at what cost—as we assess the potential help or harm of buprenorphine as a treatment for opioid use disorder.

04/21/20

Pros and Cons of Antipsychotics

Antipsychotic treatment is often associated with weight gain and metabolic syndrome, a cluster of symptoms that increases the risk of heart disease, stroke and diabetes, independent of other adverse effects like sexual dysfunction, drowsiness, dizziness, restlessness, and others. In The Lancet, Pillinger et al compared and ranked 18 antipsychotics on the basis of their metabolic side-effects. They found that antipsychotics varied widely in their effects on body weight, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and glucose concentrations. Olanzapine (Zyprexa) and clozapine (Clozaril) were ranked the worst for metabolic-related adverse effects, while ironically being identified as among the most effective antipsychotic drugs. Aripiprazole (Abilify, Aristada), brexpiprazole (Rexulti), cariprazine (Vraylar), lurasidone (Latuda), and ziprasidone (Geodon) were the most benign profiles.

In the same issue of The Lancet, Yoav Domany and Mark Weiser compared the results of this study with a network meta-analysis on the efficacy and adverse effects of antipsychotics. Clozapine was the most efficacious in reducing overall symptoms and amisulpride (Solian) was the most efficacious in reducing positive symptoms. “One would hope that data on efficacy and adverse events could be taken together with the detailed information on metabolic adverse events from this study to consider a personalized medicine approach in treating patients with schizophrenia.”

This approach could be part of a shared decision-making process, based on a discussion with the patient weighing the benefits and disadvantages of each treatment option. Such an approach is hampered by the fact that clozapine and olanzapine, which consistently come out among the best in terms of efficacy, are also consistently associated with the highest rates of metabolic adverse effects, hindering such a process at this stage.

One limitation of the Pillinger et al study was the studies in its meta-analysis were quite short, in the range of 2-13 weeks. The authors noted how randomized controlled trials are generally short and recommended that future studies should “examine antipsychotic-induced metabolic dysregulation in patients receiving long-term maintenance therapy.” Further, lifestyle and treatment factors (physical comorbidity, alcohol use, smoking, diet, exercise, and co-prescription of psychiatric—eg, mood stabilisers—or physical health medications—eg, statins or anti-glycaemic drugs) may have influenced metabolic outcomes. “Treatment guidelines should be updated to reflect differences in metabolic risk, but the choice of the treatment intervention should be made on an individual patient basis, considering the clinical circumstances and preferences of patients, carers, and clinicians.”

Standard treatment guidelines are that antipsychotic medications should continue indefinitely after someone has experienced more than one psychotic episode. But according to Sandra Steingard, there is less agreement treatment guidelines after a single psychotic episode. “Current guidelines recommend drug treatment for two to five years, the idea being that if a person remains well during that time, it might then be safe to stop the drug.” She said most psychiatrists assumed that by reducing risk of relapse you would improve long-term outcomes. But that assumption may not be correct. Not only are there risks of weight gain and tardive dyskinesia, antipsychotics seem to impair functional outcome. Robert Whitaker reported that Martin Harrow and Thomas Jobe did a long-term study of 200 psychotic patients. Patients who were off medication had better cognitive functioning and lower levels of anxiety than medicated patients. Patients on medication were more likely to be psychotic at follow-up. “Eighty-six percent of the medication-compliant patients were psychotic at the 4.5-year follow-up, compared to 21% of those who had stayed off antipsychotics. This dramatic difference remained throughout the study.” See the following chart.

Harrow also found that once patients who went off medication were stable, they were likely to remain stable for extended time periods. None of the stable, off-med patients stable at the 7.5-year follow-up relapsed in the next 7.5 years. Seventy to 90% of the unmedicated patients were working more than half time, compared to roughly 25% of the medicated patients. Those with milder disorders who continued taking medications had worse outcomes than schizophrenia patients who were off their medications.

Harrow discovered that patients off medication regularly recovered from their psychotic symptoms over time (2-year to 4.5-year outcomes), and that once this happened, they had very low relapse rates. At the same time, a majority of the patients on medication regularly remained psychotic, and even those who did recover often relapsed. Harrow’s results provide a clear picture of how antipsychotics worsen psychotic symptoms over the long term.

Schizophrenia monotherapy treatment is not always effective, and some individuals receive additional interventions, such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) and psychological therapies. Ortiz-Orendain and others conducted a Cochrane review that compared antipsychotic monotherapy and combined treatment. The authors found low-quality evidence that combined antipsychotics improved the clinical response. The study indicated that more people who received combination therapy showed an improvement in symptoms. But there were no clear differences with other outcomes, such as relapse, hospitalization, adverse events, discontinuing treatment or leaving the study early. In her review of the Ortiz-Orendain et al study for The Mental Elf, Elena Marcus said it was a well conducted systematic review. However,

One of the main limitations of this review lies in the quality of included studies, with outcomes rated as low or very low quality which really questions our confidence in the reported estimates. There was a particularly high or unclear risk of reporting bias and attrition bias across studies and as authors included quasi-randomised trials there was a risk of selection bias in ~70% of studies. Whilst five studies were clearly quasi-randomised, for 39 studies there was not enough information to judge whether sequence generation was truly random, so the risk of bias here was unclear rather than high.

Users of antipsychotic medications also describe a distinctive experience, characterized by sedation, cognitive impairment, emotional blunting and reduced motivation. These are in addition to the various physical effects, including weight gain, sexual dysfunction and neurological consequences. Thompson et al described a synthesis of qualitative data about mental and behavioral changes associated with taking antipsychotics, and how these interact with symptoms of psychosis and people’s sense of self and agency. They found that neuroleptics interfered with people’s ability to carry out basic activities. But they also reduced the intensity of intrusive psychotic experiences and other symptoms, such as anxiety and insomnia.

Anything that changes our mental faculties is likely to impact on our sense of ourselves, and this is a common experience in relation to mood or experience-modifying agents. In the studies we reviewed, some participants felt neuroleptic-induced effects deprived them of important aspects of their personality; their drives, imagination or humour, for example. Others felt that by reducing the symptoms of psychosis, the drugs were able to restore them to a state in which they felt ‘themselves’ again. Similarly, some people were content to view themselves as having a disease requiring ongoing treatment, while others felt that taking neuroleptic medication symbolised a tainted identity. Schizophrenia or psychosis can disrupt people’s sense of self, and studies of personal recovery have described the importance of reconstructing a sense of self in a way that is distinct from symptom improvement. Therefore, although neuroleptics may effectively suppress symptoms, their effects can nevertheless be experienced as detrimental to sense of self and identity, with important implications for social functioning and achievement of life goals.

John Read and Ann Sacia of the University of East London surveyed 650 individual’s experiences with antipsychotics. Two-thirds (66.9%) of the participants said their experiences with antipsychotic drugs was more negative than positive, with 34.9% stating their experiences were extremely negative. Nearly a quarter (22.1%) of the participants said their experiences were more positive than negative, with 5.7% saying their experiences were extremely positive. The authors said at the point of prescription clinicians should provide a full range of information about antipsychotics, including potential benefits and harms, difficulties withdrawing, and information on alternative treatments, such as psychological therapies.

Implied in the above critique of antipsychotics is the view that psychiatric drugs are psychoactive substances in the same way alcohol or heroin are psychoactive substances. This is what Joanna Moncrieff refers to as the ‘drug-centered’ model of drug action. Conversely, the opening study by Pillinger et al seems to view antipsychotics according to a ‘disease-centered’ model of drug action. Moncreiff said the disease-centered model is borrowed from medicine and presents drugs through the prism of disease, disorder or the symptoms the drugs are thought to treat. The significant effects (or efficacy) are the ones the drugs exert on the diseased or abnormal nervous system. Any others are of secondary interest and referred to as above as side effects or adverse effects.

In contrast, the ‘drug-centred’ model suggests that far from correcting an abnormal state, as the disease model suggests, psychiatric drugs induce an abnormal or altered state. Psychiatric drugs are psychoactive substances, like alcohol and heroin. Psychoactive substances modify the way the brain functions and by doing so produce alterations in thinking, feeling and behaviour. Psychoactive drugs exert their effects in anyone who takes them regardless of whether or not they have a mental condition. Different psychoactive substances produce different effects, however. The drug-centred model suggests that the psychoactive effects produced by some drugs can be useful therapeutically in some situations. They don’t do this in the way the disease-centred model suggests by normalising brain function. They do it by creating an abnormal or altered brain state that suppresses or replaces the manifestations of mental and behavioural problems.

The above discussion suggests individuals being treated with antipsychotics should weigh the risks and benefits of the medication prescribed to them. They need to gather information on their medication, its potential side effects and then monitor how they respond to the drug. This is consistent with what Joanna Moncrieff called the drug-centered model of drug action. The Harrow study also indicated that the use of antipsychotics may not be the best long-term treatment protocol for schizophrenia. If you are using or considering the use of antipsychotics, weigh the pros and cons.

08/26/15

The Elephant in the Room

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

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“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.

Faith Seeking Understanding

Charles Sigler, D.Phil.

Tag: drug-centered model