Letter to the Editor

Military Medicine, Dec 2003 by Bobo, William V, Grammer, Geoffrey G

To the Editor:

It is well established that antidepressive medications may precipitate manic episodes. Escitalopram, the S- enantiomer of the highly selective serotonin reuptake inhibitor (SSRI), citalopram, has been demonstrated to be effective in the treatment of depression; however, we are unaware of any existing reports of escitalopram-associated mania. Our letter describes a case of escitalopram-induced mania, with psychotic features.

A severe major depressive episode developed in a healthy 36-year-old male with no previous psychiatric history. There was no history of substance abuse, and his family history was remarkable only for depression in a primary family member. He was not taking any prescription or over-the-counter medications, herbal preparations or dietary supplements. The patient was given a trial of escitalopram, initiated at 20 mg per day. Within a few days of initiating the medication, the patient began to develop what he described as a "euphoric" mood with increasing psychomotor agitation and marked sleeplessness. Over the next week, he began to complain of a subjective sense of pressured thought, distractability, and excessive energy. The patient described pacing in his home "for hours" and came to believe that he had been chosen by divine forces to carry out a religious mission. He noted that the rapidity of his thoughts became so overwhelming that he had to place pieces of cotton into his ears in order to maintain focus. These activities resulted in psychiatric hospitalization with subsequent discontinuation of escitalopram treatment. Physical and neurological examinations were unremarkable, and vital signs were stable. A comprehensive laboratory screening battery, including TSH and urine toxicology screen, yielded no clinically significant results. Olanzipine and clonazepam were started and, within 48 hours of escitalopram discontinuation, the patient's grandiosity resolved, and full remission of his core manic symptoms was achieved by hospital day three. Serial and collateral histories from the patient, his wife and his father revealed no evidence of past mood changes consistent with mania or hypomania, or psychosis. Clonazepam was discontinued on the second hospital day, and the patient was discharged in a euthymic state on a very low dose of olanzipine, which was discontinued during outpatient treatment with no return of psychotic or mood symptoms during six months of close follow up. The patient's major depressive disorder eventually remitted using combined mirtazipine treatment and cognitive-behavioral therapy.

To our knowledge, this is the first case reported in the literature of escitalopram associated mania. Currently, it is uncertain whether antidepressant associated mania represents the unmasking of endogenous bipolar illness or a specific drug effect. Regardless, it appears that this patient's symptomatology is most consistent with mania induced by escitalopram. The clear onset and resolution of manic and psychotic symptoms associated with initiation and discontinuation of escitalopram in the absence of other chemical or medicinal exposures or family history of bipolar spectrum illness provided the most compelling evidence for a causal relationship. Conspicuous differences between the illness course observed in our patient versus that of primary manias may provide further evidence. For example, the rapid resolution of symptoms observed in this patient upon escitalopram discontinuation contrasts sharply with the typical treatment course of primary mania, even when mood stabilizing medications are administered in the earliest stages of a mood episode. Despite discontinuation of olanzipine early in the post-hospitalization phase of treatment, a rapid return of manic symptoms did not occur. The importance of this point rests in the observation that rapid return of core bipolar symptoms may develop with some consistency upon early discontinuation of other mood stabilizing medications such as lithium among those diagnosed with primary bipolar disorder. This type of an occurrence would not be nearly as likely in the context of bipolar symptoms that occurred secondary to a medication exposure, provided that the offending agent was discontinued. Finally, since secondary manic episodes have been widely observed among other serotonergic antidepressant medications, it is not all that surprising that escitalopram, another SSRI, could also be associated with such effects. Providers should be aware of this potential complication, whose etiology and incidence await further characterization.

William V. Bobo, MD

Jacksonville, Florida

Geoffrey G. Grammer, MD

Washington, DC