Do antidepressants cause manic switch?

As I said in a previous post, some critics of psychotropic medication do not always seem to apply the same rigorous scepticism to side effects as they do to treatment effects of medication. For example, in my review of Peter Breggin's (2001) The Anti-Depressant Fact Book: What Your Doctor Won't Tell You About Prozac, Zoloft, Paxil, Celexa, and Luvox, I expressed concern that people were being misled about the side effects of antidepressants. One of these controversial areas was whether antidepressants can cause people to shift to manic symptoms, potentially leading to a diagnostic transition from unipolar depression to bipolar disorder. 

Ironically, mainstream psychiatry also tends to believe in a causal relationship between antidepressants and manic switch (see eg. previous post). Current guidelines do not recommend using antidepressants in first-line treatment for acute bipolar depression, at last partly because of the risk of manic switch (see recent American Journal of Psychiatry editorial). Even so, generally the evidence for antidepressant induced mania has been seen as uncertain.

Rhode et al (2024) used data from a Danish health register to compare the occurrence of mania and bipolar depression in the year after discharge from a psychiatric ward of bipolar depressed patients who either received antidepressants or did not. There was no statistically significant association between treatment with an antidepressant and the risk of mania in the full sample, nor in the subsample concomitantly treated with a mood-stabilizing agent, nor in the subsample not treated with a mood-stabilizing agent. Neither was there any statistically significant association between treatment with an antidepressant and bipolar depression recurrence. This study may add to those questioning whether the risk of manic switch is overblown.

Another recent study (Tondo et al, 2024) found that about 6.7% of patients initially diagnosed as unipolar depression followed over a period of a mean of 12.7 years had their diagnosis changed to bipolar disorder, mostly type II (76.7%) rather than type I. This conversion rate may not be as high as expected, considering the fears of manic switch. 

Moreover the way in which the concept of bipolar disorder has expanded over recent years (see eg. previous post), in association with the introduction of mood-stabilising medication (see eg. another previous post), highlights how malleable psychiatric diagnosis is. There is a legitimate issue about what bipolarity means when it has become such an all embracing term, essentially amounting to mood instability, which of course is very common and not always necessarily best described as a mental disorder (see eg. yet another previous post). The mechanism of manic switch is unclear, and psychogenic, rather than physiological factors, may be significant. A sceptical approach to interpreting the inconsistent evidence is required. Manic switch is a risk in the use of antidepressants but how significant this is and whether it is physically caused remains uncertain.