Tofranil Not Ideal for Treating Bipolar

People diagnosed with bipolar experience dramatic fluctuations in their mood states, ranging from profound and debilitating depression to mania. Mania is characterized by intense energy, activity, euphoria, and even aggression. Episodes of mania complicate treatment because patients suffering a manic state are often resistant to treatment and don’t follow their medication regimen. Most individuals who have bipolar experience depression more often, and for longer periods than mania.

However, antidepressant medications have the unfortunate effect of altering the person’s mood from depression to full-blown mania, a phenomenon known as “switching.” Scientists believe that subtle biochemical processes are somehow responsible for this effect. Current research is focused on why switching happens, along with the potential therapies that might prevent it.

In a study conducted at the National Institutes of Health in Bethesda, Maryland, the antidepressants Tofranil (imipramine) and Wellbutrin (bupropion) were investigated for their potential to cause switching in bipolar patients. Tofranil is classified as a tricyclic antidepressant, while Wellbutrin’s molecular structure makes it unique. Groups of rats were treated with one of these medications or placebo. Some received daily doses while others received a single dose before being euthanized. Rats administered either of the medications displayed increased activity, and post-mortem examinations revealed evidence of an antidepressant effect.

With Toranil, there were increased levels of a specific chemical called arachidonic acid that researchers have linked to bipolar switching. Blood testing and brain examinations revealed much lower levels of this chemical in the brains of rats given Wellbutrin. Rats that received an acute rather than a chronic dose showed no significant changes over the control group, proving that the effects require repeated dosing to become realized.

Currently, treatment of bipolar often involves a delicate balance between an antidepressant medication, a mood leveler like lithium to prevent mania, and cognitive behavioral therapy. Tofranil appears to have the same potential to cause switching as newer antidepressants like Prozac (fluoxetine). Wellbutrin, on the other hand, has an entirely different structure and mechanism of action. Medications like Tofranil, therefore, should probably be avoided for the treatment of bipolar disorder. Ultimately, a better understanding of the dynamics of bipolar disorder will lead to treatments that are more effective with fewer unwanted effects.


  1. Bipolar disorder – PubMed Health. (n.d.). National Center for Biotechnology Information. Retrieved May 1, 2012, from
  2. Bupropion – PubMed Health. (n.d.). National Center for Biotechnology Information. Retrieved May 1, 2012, from
  3. Imipramine – PubMed Health. (n.d.). National Center for Biotechnology Information. Retrieved May 1, 2012, from

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