Can Antidepressants Make You Bipolar?

Bipolar disorder is a spectrum disorder characterized by at least one manic or mixed episode, alternating (typically) with depressive episodes. It conforms to Kraepelin's original concept of manic-depressive illness, which can include psychosis symptoms during mood episodes. In bipolar I, you see swings between manic and depressive episodes; in bipolar II disorder the individual never experiences a full manic episode but instead exhibits less severe hypomania (which has the expansiveness of mania but lacks the delusional grandiosity). There's also a somewhat controversial diagnosis of Cyclothymic Disorder, which refers to a serious lability of mood that (for whatever reason) fails to meet the diagnostic requirements of bipolar.

On Showtime's Homeland, Claire Danes (left) played a bipolar CIA agent.
(Mandy Pitinkin, right, played opposite her as a CIA higher-up.)

Despite bipolar's depiction in modern culture as being somewhat common, it's actually quite rare. Bipolar disorder occurs naturally (in the U.S.) at a lifetime rate of 4%. That figure turns out to be quite a bit higher than the condition's actual worlwide prevalence (rate of actual occurrence at any given moment). The World Mental Health Survey initiative found a prevalence of bipolar II in the population of eleven countries to be 0.4%, making it less common than schizophrenia. The prevalence rates of bipolar I and II are thought to be comparable. In the U.S, each occurs with a prevalence of about 1%.

The Diagnostic and Statistical Manual of Mental Disorders (5th Ed.), in its formal criteria for bipolar, discounts mania as mania (or as hypomania) if it's induced by drugs, which is extraordinarily convenient, in that antidepressant drugs can and do cause hypomania in some people. I say "convenient" because the drug companies are keenly interested in dispelling the notion that (unipolar) depressed patients who start taking antidepressants are often, in so doing, converted to bipolar patients, which is exactly what does happen at several times the spontaneous rate.

In a literature review of 51 studies involving nearly 100,000 patients with MDD without a history of mania or hypomania who were treated with an antidepressant, Baldessarini et al. (2013) found bipolar mood switching occurred in 8.2% of patients within an average of 2.4 years of treatment. They also said: "We considered 12 studies of patients initially thought to have unipolar MDD who required a new diagnosis of bipolar disorder, usually with verification by occurrence of spontaneous mania or hypomania. Such diagnostic changes occurred in 3.3% within 5.4 years, or 5.6 times less than the rate of mood switching with antidepressants."

What it means is that if you go to your doctor with major depressive disorder (unipolar depression) and start taking antidepressants, there's an 8.2% chance you'll be bipolar within 2.4 years. Some people react to antidepressants by going manic or hypomanic. It may not happen in the majority of cases, but it is a significant chance, and the longer you're on antidepressants, the greater the chance of a changeover to bipolar.

From personal experience, I can tell you that if your daily routine includes coffee in the morning and alcohol at night, you stand a much better chance of avoiding the bipolar switch if you cut alcohol out of your life completely and keep coffee and other stimulants under control. Coffee and alcohol are cyclothymia triggers (potentially). You want to moderate their effects.

What happens if you do experience mania? Is there a known-good way to treat it? Actually, there is. It's called lithium carbonate, and it's one of the best proven, least expensive anti-mania treatments money can buy. It's also fast-acting and can be taken "PRN" (which means as needed), although it's rarely prescribed that way. The problem with lithium is that today's doctors are using 50-year-old dosing recommendations that often result in a patient taking toxic amounts of the stuff. A typical dosing regimen is 450 mg two to three times a day. That kind of dose will make you toxic in a couple of weeks, but unfortunately, there are few modern studies involving lower-dose lithium. One such study that's worth considering is Alevizos et al. (2012), which looked at the response to adjunctive low-dose lithium in 47 severely depressed patients who failed to respond to venlafaxine (Effexor) alone. Said the researchers: "After 5 weeks of augmentation, 51% of the patients were rated as 'much' or 'very much' improved. Bipolar patients showed a better response than unipolar (64.3% vs 45.5%, p<0.038). Most patients (76%) showed a rapid response (up tp 7 days)."

Two things need to be mentioned with regard to the Alezivos study. First, there was no placebo control arm, hence the results await validation by a properly controlled, properly blinded study. Secondly, "low dose" here meant 300 to 450 mg per patient per day (corresponding to about 5 mg/kg), which is still a high dose. Modern medical science still hasn't wrapped its head around the idea that you can benefit from low doses of lithium, even though we have tantalizing evidence (see, for example, this study; there are others) that micromolar concentrations of lithium in tap water can prevent suicide.

Much of the information in this post was taken from a 110,000-word book I'm writing on mental illness. To follow the book's progress, add your name to the mailing list and return to this blog often. Thanks!