What to Ask Before Your Next Antidepressant Prescription

Questions for Your Doctor Series

The STAR*D trial cost $35 million and enrolled over 4,000 patients. It was the largest antidepressant effectiveness trial in the history of psychiatry. The investigators announced that approximately 70 percent of those who stayed in the study became symptom-free. That figure entered textbooks, training materials, and patient handouts. Most patients prescribed an antidepressant today are being prescribed a drug whose evidence base rests substantially on this number.

Ed Pigott and colleagues spent more than five years analysing the underlying data. Once dropouts and relapses during follow-up were properly accounted for, the figure that answered the question STAR*D was designed to answer — patients who entered the trial, achieved remission, stayed well, and remained in follow-up at one year — was 3 percent. Confronted with the figure, investigator Maurizio Fava acknowledged it was accurate. The investigators had known all along.

Seventy percent was the number that entered textbooks and patient handouts. Three percent was the number the trial actually produced. By 2007, nearly four million Americans were receiving federal disability payments due to mental illness — a sixfold increase during the era of greatest antidepressant prescribing expansion in history.

The story patients hear in a ten-minute consultation — chemical imbalance, biological vulnerability, lifelong management — has been contradicted by the profession’s own research. The 2022 systematic umbrella review in Molecular Psychiatry found no consistent evidence of a serotonin-depression link. Steven Hyman, the former director of the National Institute of Mental Health, acknowledged that patients do not start with chemical imbalances. The drugs create them. The brain compensates for the presence of the medication by altering its own chemistry, which is why so many patients cannot get off the drug once they start. As many as half of those who attempt to stop experience withdrawal symptoms — dizziness, electric shock sensations, agitation, depression — that the patient and the prescriber both misinterpret as the depression returning. The drug is restarted. The symptoms vanish within hours. A real depressive episode does not respond to a pill within hours. The Royal College of Psychiatrists, after decades of denial, acknowledged in 2019 that SSRI withdrawal can be severe and prolonged.

The document is a 13-page formatted guide — ten questions with their Key Facts, two paragraphs of context behind each, a routing table to find the questions that match your situation, and a one-page Quick Reference to print and take to the appointment.

Here is Question 4, one of the ten:

Question 4: What is the documented risk that an antidepressant will trigger mania and convert me into a long-term bipolar patient?

Key Fact: A Yale study of 87,290 patients diagnosed with depression or anxiety found that those treated with antidepressants converted to bipolar illness at a rate of 7.7 percent per year — three times the rate for those not exposed to the drugs. Over longer periods, 20 to 40 percent of patients initially diagnosed with unipolar depression eventually convert to bipolar.

The first report of antidepressant-induced mania appeared in 1956. In 1993, the American Psychiatric Association’s own practice guide for depression conceded that “all anti-depressant treatments, including ECT, may provoke manic or hypomanic episodes.” The Yale data from 2004 quantified the rate: 7.7 percent of antidepressant-treated patients converted to bipolar each year, three times the rate observed in unexposed patients. In a survey conducted by the Depressive and Manic-Depressive Association, 60 percent of those carrying a bipolar diagnosis reported they had initially been depressed and turned bipolar only after antidepressant exposure. Fred Goodwin, co-author of the field’s standard textbook Manic-Depressive Illness, described the mechanism in a 2005 interview: “If you create iatrogenically a bipolar patient, that patient is likely to have recurrences of bipolar illness even if the offending antidepressant is discontinued.”

One context paragraph above. A second, going deeper into the mechanism and the implications, sits inside the document along with the other nine questions.

The other nine cover the chemical imbalance theory, the absolute effect size of SSRIs over placebo, the active placebo problem, what SSRIs do to emotional and cognitive function, the withdrawal mechanism that traps patients on the drugs, the long-term outcome data showing medicated patients fare worse than unmedicated ones, the STAR*D reanalysis, and the non-pharmaceutical approaches that address what is actually driving the symptoms.

The evidence in this instalment is drawn from three essays at Lies are Unbekoming — “Feeling Better, Getting Worse: How Psychiatric Drugs Create the Illusion They Cure,” “Bipolar: The Manufactured Epidemic,” and “The Top 10 Myths of Modern Psychiatry” — which assemble work from Peter Gøtzsche (Mental Health Survival Kit; Is Psychiatry a Crime?), Peter Breggin (Toxic Psychiatry; Talking Back to Prozac), Irving Kirsch (FDA data analysis of the major SSRIs), Robert Whitaker (Anatomy of an Epidemic), Joanna Moncrieff (The Myth of the Chemical Cure), Mark Horowitz and David Taylor (hyperbolic tapering, Lancet Psychiatry), Giovanni Fava (long-term sensitisation), and Ed Pigott (the STAR*D reanalysis).

If you or someone you know has an appointment coming up — yours or a family member’s, a first prescription or a long-term review — print the Quick Reference page and take it with you.

If there is a screening test, a prescription, or a procedure where you needed the right questions before you walked into the room, put it in the comments. The next topics will come from what you need most.

A paid subscription unlocks the full Questions for Your Doctor series — every instalment as it publishes, the back catalogue of guides already available, and the underlying books and essay summaries that make the case in depth.

Antidepressant Prescription: Questions for Your Doctor is available for download below.