Trimipramine For Refractory Panic Attacks

David Ginsberg, MD

Dr. Ginsberg is Director of Outpatient Services, Tisch Hospital’s Department of Psychiatry, New York University Medical Center

Trimipramine is a tertiary amine tricyclic antidepressant (TCA) chemically related to imipramine, which was the first drug shown to be effective for the treatment of panic disorder. In general, TCAs are not widely used today because of the superior safety and tolerability profiles of selective serotonin reuptake inhibitors (SSRIs).

Now comes a report on the successful use of trimipramine in a panic disorder patient who had not responded to SSRIs.

A 41 year-old white man suffered from panic attacks since the age of 21 years. Past trials of multiple psychotropic agents, singly and in combination, were either intolerable or ineffective and included: amitriptyline, bupropion, amoxapine, fluoxetine, sertraline, citalopram, paroxetine, fluvoxamine, duloxetine, escitalopram, carbamazepine, valproic acid, lithium, olanzapine, aripiprazole, olanzapine plus fluoxetine, aripiprazole plus fluoxetine, clonazepam, lorazepam, alprazolam, and combinations of alprazolam with multiple SSRIs, atypical neuroleptics, tricyclics, tetracyclics, and anticonvulsants. At the time of presentation, the patient was taking fluoxetine 20 mg/day, alprazolam 8 mg/day, and olanzapine 10 mg/day. Despite this, he continued to experience 1-2 panic attacks every 10 days. He had been taking alprazolam for 14 years.

At this point, fluoxetine and olanzapine were discontinued while mirtazapine 15 mg hs was added to the longstanding alprazolam 2 mg/day. Due to stimulatory effects, mirtazapine was discontinued. Quetiapine 25 mg/day was added but later had to be discontinued due to gastrointestinal side effects. Next, desipramine was started at 10 mg hs, then increased over the next 2 weeks to 20 mg hs. Due to overstimulation and worsening of panic attacks, desipramine also had to be discontinued. While maintaining the alprazolam constant at 2 mg/day, trimipramine 25 mg/day was started, then increased to 50 mg every day in the morning. Over the following 5 weeks, the patient indicated that he felt “much calmer” and that he had not experienced any further panic attacks. Furthermore, he remained panic-free over the next 6 months during which time tapering of alprazolam had been initiated.

While SRIs remain the mainstay of panic disorder therapy, for treatment-resistant patients, TCAs such as trimipramine still have a place in the psychopharmacologic armamentarium.