Pramipexole in the Treatment of Refractory Depression in a Patient with Rapid Cycling Bipolar Disorder.

Sir,

Bipolar depression offers significant treatment challenges since this condition is associated with treatment resistance as well as potential risk of “switching” to mania/hypomania with treatment.[12] The presence of rapid cycling-course offers added substantial therapeutic challenge with limited number of safe therapeutic options. Pramipexole, a dopaminergic agonist has been evaluated in treatment resistant depression[3] and it probably works with a distinct dopamine based neural mechanism.[4] However, its use in bipolar depression resistant to multiple therapeutic options in the context of rapid cycling disorder has not been reported.

Mr. S, a 37-year-old businessman with a 12-year history of bipolar II illness, in the initial 10 years of the course of the illness, had 13 episodes of depression and 7 episodes of hypomania. In the latter 2 years, he had multiple depressive episodes and 1 episode of hypomania. The depressive episodes would last between 2 weeks and 4 months while hypomanic episodes would last between 1 week and 2 months. The most recent was an episode of severe depression along with catatonic symptoms (ICD-10) which continued for 7 months despite adequate treatment with lithium carbonate and lamotrigine, olanzapine and fluoxetine and 2 sequential adequate trials with antidepressants [sertraline (upto 150 mg) and escitalopram (20 mg) (both under the cover of lithium carbonate)]. He received lorazepam up to 6 mg per day for 2 weeks, for the catatonic symptoms without significant benefit. He also received 3 bitemporal Electro Convulsive Therapy (ECT) which was discontinued due to prolonged post-ictal confusion.

In addition to the existing treatment regimen consisting of lithium carbonate 900 mg/day (serum lithium level-0.8 meq/L), lamotrigine 150 mg/day and olanzapine 10 mg, pramipexole was introduced. The dosage was initially at 0.125 mg per day, hiked up to 0.5 mg per day in two divided doses over 2 weeks. Mr. S reported significant improvement in symptoms from the second week of initiation of pramipexole. His mood improved along with significant improvement in psychomotor activity and catatonic symptoms. The Hamilton Depression Rating Scale (HDRS) score improved from 22 to 7 by the end of 1 month of treatment. The Bush-Francis Catatonia Rating Scale (BFCRS) scores reduced from 8 to 0 during the same period. This clinical improvement was confirmed through independent assessment by two psychiatrists. The improvement persisted until the latest review 2 months after starting pramipexole and he has not reported any adverse effects with the drug.

DISCUSSION

There are small randomized-controlled trials and open-label studies.[35] supporting the efficacy of pramipexole in resistant bipolar depression. However, in majority of these studies, “resistance” indicates failure to respond to one or two medications. The improvement in depression “refractory” to multiple treatment options as shown in this case is note-worthy. Pramipexole did not cause adverse effects in the index patient, in particular, “switch” to hypomania, an important concern in the context of rapid cycling course. Considerable improvement was observed in many domains including catatonic symptoms. Hence, pramipexole augmentation appears to be a safe and effective treatment strategy in bipolar depression when conventional treatment options fail.