The Bitter Pill

(Originally published September 2019)

The April 8th issue of The New Yorker contains an article by Rachel Aviv regarding the multiple side effects of psychotropic drugs, and the difficulty of discontinuing their use even when the drug or (more often) drugs are doing demonstrable harm. This article tells the story of Laura Delano, a young woman diagnosed with bi-polar disorder in her late adolescence, who subsequently (in stages) was prescribed increasingly larger doses of Prozac and then Provigil, to counteract the drowsiness resulting from taking Prozac, Ambien, to counteract the effects of Provigil on sleep, and then, after a stay in a mental hospital, a new combination of drugs, including Lamictal (a mood stabilizer) Lexapro (an antidepressant), and Seroquel (an anti-psychotic), used as a sleep aid. This sounds more like a horror movie than medicine, but (alas) not so. Over the next few years her doctors tripled her antidepressant dosage and quadrupled her dosage of Lamictal. She began taking Klonopin, a benzodiazepine, as a sedative. After a suicide attempt and hospitalization, she was put on a new combination of drugs, including a second antipsychotic, Abilify. Other therapists diagnosed this young woman as borderline personality after dismissing her bi-polar diagnosis. Some of these drugs caused large weight gain, suppressed sexual desire, and left her feeling empty and damaged.

 

Ms. Delano then came across Robert Whitaker’s book, Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America (2010), which motivated her to gradually reduce the use of these drugs. Reducing and then eliminating the use of psychotropic drugs turned out to be exceedingly difficult. After she stopped using Abilify, “She began sweating so much she could only wear black. If she turned her head quickly, she felt woozy. Her body ached, and occasionally she was overwhelmed by waves of nausea. Cystic acne broke out of her face and neck. Her skin pulsed with a strange kind of energy. I never felt quite in my body ...”, Ms. Delano told the reporter. When she stopped using Effexor, her fear of people increased, and she felt that others viewed her as loathsome. She became a couch potato who watched TV all day. Aviv quotes a pharmacological expert, David Taylor regarding his personal experience when he stopped using Effexor, “a strange, frightening and tortuous experience” that took 6 weeks.

 

This young woman suffered through a terrible experience (which others might have viewed as evidence that she needed to be on a heavy drug regimen) and eventually eliminated the use of psychotropics. According to the story, she regained her sexuality (which she had never experienced in adolescence or young adulthood) and was able to develop and maintain intimate interpersonal relationships. She has become a guide to others attempting to dispense with psychotropic drugs. Aviv asserts that there is little science or reliable guidance on how best to eliminate use of these drugs which, for some people, is akin to a life sentence of drug dependence and diminished capacities. Aviv writes: “For many people … it was impossible to separate the bio-chemical repercussions from the social ones. The medicines worked on their bodies, but they changed the way people understood their relationships and their social roles, and the control they had over elements of their lives … people felt that at some point having taken so many medications for so long, they’d become disabled - and they were no longer sure this was due to their underlying disorder, the effect of withdrawing from their medications, or the way they had internalized the idea of being chronically ill.“ In stories of heavily medicated persons contained in Anatomy of an Epidemic, it was common for psychiatrists to inform patients of all ages that they would need to take prescribed drugs their entire lives, just as a diabetic needs to take a daily dose of insulin!

 

Aviv comments that “there are almost no studies on how and when to go off psychiatric medications, a situation that has created what one expert calls “a national public health experiment.” Unfortunately, foster children and youth are very much a part of this experiment, which adds to the formidable challenges of their young adulthoods. I challenge any reader who has contact with older foster youth or foster care alumni to ask these young people if they believe the psychotropic drugs they were prescribed in their childhood or adolescence helped or harmed them, and if they continued taking these drugs after exiting foster care.

 

Diagnosing mental health conditions

 

Biologically oriented psychiatrists have been quick to prescribe powerful biological agents designed to correct chemical imbalances in the brain (a scientific fiction discussed in last month’s Sounding Board) based on diagnoses contained in several editions of the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM). According to Anne Harrington’s recent book, Mind Fixers, the DSM-III which was published in 1980, “effectively expunged all, or almost all, psychoanalytic language … They (the developers) intended the new DSM to be concerned only with descriptive diagnostics and not with etiology. Of course, they were being disingenuous. They believed that biological - not psychoanalytic - markers and causes, would eventually be discovered for all the true mental disorders.” The DSM uses checklists of symptoms to achieve a high level of reliability in diagnosis. Harrington comments: “… improved rates of what the DSM architects called “inter-rater reliability” did not mean that the disorders themselves were valid. One could easily imagine a group of medieval exorcists all agreeing that certain symptoms – say convulsions – should lead to a diagnosis of demonic possession. That did not mean demonic possession really existed.”

 

The developers of DSM-III anticipated that rejection of psychoanalysis and the embrace of a psychiatry based on science would lead to the discovery of biomarkers for major mental illnesses. However, in 2013 following the release of DSM-5 “something quite extraordinary happened,” Harrington asserts. “The director of NIMH (National Institute of Mental Health) … (Tom Insel) drew a clear red line between the new edition and the institute’s research activities. NIMH, he said. “will be reorienting its research away from DSM categories…” Harrington adds that “For years, Insel had been critical of the DSM, insisting that the so called “bible of psychiatry”’ had 100 percent reliability and 0 percent validity.” According to Insel, “biology never read that book (the DSM).”  More than 30 years after publication of DSM-III, biomarkers for mental illnesses as described by the DSM had not been discovered.  

 

Psychiatrists use DSM checklists to diagnose the existence of mental health conditions (viewed as brain diseases) that do not have biomarkers, and then prescribe powerful drugs to combat these conditions. The idea that use of the DSM leads to reliable mental health diagnoses in children is highly questionable. Just as in The New Yorker story, foster children and youth may receive several diagnoses sequentially, often beginning with ADHD, followed frequently by bi-polar disorder, anxiety and depression, oppositional defiant disorder and, in extreme cases, by autism or schizophrenia. Each new diagnosis may lead to a new psychotropic medication. I have reviewed cases during recent years in which children as young as 4-6 have multiple diagnoses and are on cocktails of stimulants, antipsychotics, antidepressants and sleep aids. Medications are more likely to be added than subtracted as psychiatrists hear about the child behaviors caregivers are most concerned with at the time.

 

Mistaken mental health diagnoses can lead to great suffering of both children and adults. In her memoir, Giving Up the Ghost, the novelist, Hilary Mantel, describes the effects of medications she was

prescribed in the 1970’s after her physician decided her physical complaints were psychosomatic. She was first prescribed a tricyclic antidepressant which had little effect. She was then given Valium which caused her to be enraged; she began to fantasize about harming people, including strangers. Her psychiatrist then prescribed an antipsychotic, Fentazine. Mantel writes:

 

Do you know about akathisia? It is a condition that develops as a

side effect of antipsychotic medication … it looks, and it feels like

madness. The patient paces. She is unable to stay still. She wears

a look of agitation and terror. … she says she is in hell.

 

… Akathisia is the worst thing I have ever experienced, the worst

single defined episode of my entire life… No physical pain has ever

matched that morning’s uprush of killing fear, the hammering heart

You choke; pressure rises inside your skull. Your hands pull at your

clothing and tear at your arms … you want to hurl yourself against

windows and walls. Every fiber of your being is possessed by panic.

Every moment endures for an age …

 

 

Hilary Mantel was in her twenties when she had these experiences, and she was gifted with language. What would likely occur if a school age foster child with poor language skills and a distrust of caregivers had similar experiences? How could the child protect herself/himself except through difficult “crazy” behavior which might lead to the prescription of another medication to combat the panic attack?

 

The use of antidepressants with children and youth

 

The use of selective serotonin reuptake inhibitors (SSRI) anti-depressants with children and adolescents has been controversial since the early 2000’s when the British counterpart of the Federal Drug Administration (FDA) warned against the use of SSRI’s (with the exception of Prozac) to treat adolescents with major depressive disorder based on clinical data contained in drug trials, data which suggested that SSRI’s increased suicidal ideation and behavior in some percentage of adolescents taking these drugs. In October 2004, after a review of clinical trial data in possession of drug companies, the FDA issued a ‘black box’ label warning that all SSRI’s may increase suicidal ideation with some depressed adolescents. According to an author critical of the FDA warning, “the black box is the most severe warning the FDA can place on a drug, short of an outright ban.” In 2006, the FDA expanded the warning to include young adults from 18-24.

 

In Anatomy of an Epidemic, Whitaker asserts that by the late 1980’s there were “numerous anecdotal reports of Prozac treated patients committing horrendous crimes or killing themselves, … By the summer of 1997, the FDA had received thirty-nine thousand such reports about Prozac, far outstripping the number received by any other drug for that nine-year period (1988-1997).” Given this information, I was surprised to discover that some researchers maintain that the use of SSRI’s with adolescents reduces, rather than increases, suicide rates among adolescents, claims based on population studies and post-mortem studies rather than clinical trials, which indicate the opposite.

 

Given this difference of scholarly opinion on such an important issue, I looked for a recent comprehensive review of research on the use of antidepressants for child and adolescent depression by scholars who support such use, and who believe SSRI’s reduce rather than increase suicidality in moderately to severely depressed adolescents. I found such an article by Gardner, et al, titled “Update on the use of SSRI’s and SRNI’s with children and adolescents in clinical practice,” (2016) in a Canadian psychiatric journal. Some of the main conclusions in this dispassionate (but highly debatable article) include:

 

  • “The majority of (drug) trials were unable to demonstrate a measurable difference in the a priori (predetermined) main endpoint of the trial,” presumably a reduction of depressive symptoms.

  • Considering the evidence as a whole, a few SSRI’s such as fluoxetine, i.e., Prozac, (but not SNRI’s) have small to moderate effect sizes in 6 to12 week clinical trials, although these authors acknowledge that early trials of Prozac employed the “placebo washout” effect, i.e., eliminating persons in the trial who showed an early reaction to placebo. Two more recent trials which did not employ “placebo washout” did not find Prozac to be more effective than a placebo. A small to moderate effect size is described as 1 in 4 to 1 in 10 adolescents who do better on Prozac than placebo.

  • Placebos reduce depression in about 50% of adolescents.

  • “No SSRI or SSNI (i.e., drugs that target norepinephrine such as Effexor) consistently demonstrate positive results for depression with prepubertal children.”

  • There are very few longer-term continuation studies available; the small number of such studies continue to demonstrate symptom relief for SSRI’s at 36 weeks.

  • “No antidepressant has been shown to be superior to placebo in achieving (reduced) remission rates …”

  • Cognitive Behavioral Therapy (CBT) has about the same rates of effectiveness as SSRI’s, though studies of CBT have been less rigorous than studies of SSRI’s.

  • In short term drug trials, 10-25% of adolescent experience negative physical and/or emotional side effects, including headaches, gastric distress, insomnia or hypersomnia, hyperactivity, irritability, hostility, disinhibition, emotional lability and self-harm. These side effects are only modestly elevated over placebo.

 

  • Two in 100 adolescents taking SSRI’s experience an increase in suicidality vs. 1 in 100 youth who take a placebo.

  • There is no clear research answer to the question of whether antidepressants increase the risk of bi-polar disorder; no evidence regarding any other long-term negative effect on physical health or mental health is mentioned.

 

  • An antidepressant should not be the initial therapeutic response to adolescent depression, and when antidepressants are prescribed for persistent moderate to severe depression, SSRI’s should only be used in conjunction with psychotherapy. Any prescription of an SSRI should be followed up within a week by the therapist or psychiatrist to check on suicidal ideation.

  • SSRI’s have “substantial benefits” for some adolescents despite the risk of side effects, presumably because other therapeutic interventions have not been effective.  

 

There is no mention in this article of research regarding interactions between antidepressants and other classes of psychotropic drugs such as stimulants or antipsychotics. There is no discussion regarding guidelines for helping adolescents stop using SSRI’s when the drugs have negative side effects. There is not a single word regarding the self-healing capacities of the human mind and body independent of the placebo effect, no acknowledgment that depression often goes away without any intervention.   

 

Gardner, et al, have made the best case for use of SSRI’s with severely, persistently depressed adolescents that can be made given recent research, but it is a case that has large gaps in knowledge and understanding regarding long term effects of these drugs. As with other classes of psychotropic drugs, many psychiatrists and caregivers have been so impressed with SSRI’s short-term reduction of gravely disabling symptoms that questions regarding long term effects have been pushed aside. Patients’ stories regarding the disastrous effects of months and years of drug use have been minimized, rationalized and sometimes used to justify increasing dosage or adding new medications. 

 

 

 

References

 

Aviv, R., “The Bitter Pill,” The New Yorker, April 8, 2019.

 

Harrington, A., Mind Fixers: Psychiatry’s Troubled Search for The Biology of Mental Illness (2019). W.W. Norton & Company, New York City.

  

Ho, D., “Anti-depressants and the FDA’s Black Box Warning: Determining a Rational Public Policy in the Absence of Sufficient Evidence”. AMA Journal of Ethics, Policy Forum, June 2012. 

 

Garland, E., Kutcher, S., Virani, A., Elbe, D., “Update on the Use of SSRI’s and SRNI’s with Children and Adolescents in Clinical Practice,” Journal of the Canadian Academy of Child and Adolescent Psychiatry, 25 (1), Winter 2016.   

 

Mantel, H., Giving Up the Ghost: A Memoir (2003). Henry Holt & Company, New York City. 

 

Whitaker, R., Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America (2010). Crown Publishers, New York City.

 

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