Traditional Antidepressants Are Not Effective in Bipolar Depression

July 11, 2014 · Posted in Current Treatments 

man taking an antidepressantBipolar illness affects 4.5% of the US population. According to researcher Kathleen Merikangas, 1.0% have bipolar I disorder, 1.1% have bipolar II disorder, and the remainder have subthreshold symptoms. Mark Frye, Chairman of the Department of Psychiatry at the Mayo Clinic, gave a lecture on antidepressants in bipolar illness at the 2014 meeting of the American Psychiatric Association.

The newest data from meta-analyses indicate that traditional antidepressants that are effective in unipolar depression are not effective in bipolar depression. Some patient groups, especially those with very early onset depression and mixed depression, are at increased risk of switching into mania and making a suicide attempt while taking antidepressants.

Unipolar depressed patients with a genetic variation that produces a short form of the serotonin transporter (5HT-LPRs/s) are at increased risk for depression in adulthood following a history of childhood adversity, and tend to respond less well to antidepressants. Frye found that 5HT-LPRs/s is weakly associated with switching into mania when antidepressants are given to patients with bipolar depression.

At the same symposium, researcher Mike Gitlin reviewed data on combination therapy, which is rapidly becoming the norm, indicating that in most circumstances, it is superior to monotherapy.

Researcher David Miklowitz reviewed the impressive data on the superiority of most forms of targeted psychotherapy or psychoeducation compared to treatment as usual for bipolar depression. He noted his own finding that Family Focused Therapy (FFT) not only is effective in adolescents and adults with bipolar disorder, but also in reducing illness and dysfunction in those with prodromal disorders (such as depression, cyclothymia, and bipolar not otherwise specified) in situations where there is a family history of bipolar disorder.

Eight components of FFT are:

  1. Recognition of prodromal symptoms and development of treatment strategies for them.
  2. Recognition and management of stress and triggers using cognitive restructuring.
  3. Development of a relapse prevention plan and rehearsal of what to do.
  4. Regularization of sleep.
  5. Encouragement of treatment adherence with an eye to a good future.
  6. Enhancement of emotional self-regulation skills, including cognitive restructuring.
  7. Improvement of family relationships and communication.
  8. Education about substance abuse avoidance and treatment for that and other comorbidities.

Many of these are also key components of group psychoeducation, cognitive-behavioral therapy, and interpersonal and social rhythms therapy, and all of these are effective in treating and preventing bipolar depression compared to treatment as usual. It is noteworthy that in the research of Francesc Colom, 90% of patients randomized to treatment as usual relapsed within 24 months, while psychoeducation was highly effective in preventing relapses over the next five years.

This editor (Robert M. Post), the discussant for the symposium, emphasized that the main take-away messages of the speakers were: use more lithium, use more caution and fewer antidepressants in treating bipolar depression, use more combination therapy for acute illness and for maintenance, and definitely use more psychotherapy.

Editor’s Note: I also emphasized the more severe illness characteristic of patients with bipolar disorder from the United States than from many countries in Europe, and that this demands revisions in our typical treatment practices. Early onset of illness and delay in time to first treatment are both independent predictors of a poor outcome in adulthood, indicating the need to intervene earlier and more effectively in the two-thirds of patients with bipolar disorder from the US who have onsets in childhood and adolescence (before age 19).

There is a kindling-like process in the illness, where recurrent episodes yield more rapid relapses and episodes that begin to occur without precipitating stressors. There is sensitization, or increased reactivity to repeated stressors, episodes, and bouts of substance use, which all induce illness progression. Greater numbers of prior depressions are associated with cognitive dysfunction, treatment resistance, medical comorbidities, and neurobiological abnormalities, including shorter telomeres and even dementia in old age. Thus, preventing the onset of new episodes becomes the primary goal of treating bipolar disorder.

Preventive intervention must be introduced earlier and more consistently in order to try to reduce the pernicious course of bipolar disorder, particularly in the US. I would definitely recommend family focused therapy for early symptoms in children at high risk for bipolar disorder by virtue of a positive family history. My new mantra is:

“Prevent episodes and protect the body, the mind, and the brain.”  (Lithium, in combination with other agents and psychotherapy, is one of the best ways to do this in patients with bipolar disorder.)


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