Pregabalin Augmentation to Sertraline-Risperidone Combination in the Treatment of Obsessive-Compulsive Disorder

Abstract

Sir: Despite the marked progress in the pharmacologic treatment of obsessive-compulsive disorder (OCD)—espe- cially with high doses of serotonin reuptake inhibitors (SRIs), alone or in combination with low doses of antipsy- chotics—a substantial proportion of patients fail to respond to it. 1 In such cases, an augmentation tactic with drugs from other chemical classes, including antiepileptic drugs, seems advisable. We report on such a case, in which the adjunction of the newer antiepileptic drug pregabalin led to a patient's marked improvement. Case report. Ms. A, a 35-year-old woman, had suffered from OCD according to DSM-IV criteria 2 since the age of 3 with an overall severity scale score of 4, whereas on the Hamilton Rating Scale for Anxiety (HAM-A), 4 she scored 27. Both sertraline and risperidone were maintained at the previously mentioned dosages, whereas clobazam was dis- continued. Pregabalin was added to her regimen instead and titrated up to 600 mg/day within 3 weeks. Dizziness and fatigue were the only transient side effects of pregabalin. During pregabalin treatment, Ms. A's mental and behavioral state improved progressively, and at discharge, 12 weeks later, her scores on the YBOCS and HAM-A had dropped by almost 55% and 40%, respectively. More precisely, her YBOCS score dropped to 16, with an overall severity score of 2 and an overall improvement score of 5, and her HAM-A score dropped to 15. Of note, the patient's level of improve- ment was wholly preserved at her last outpatient appoint- ment 6 months later. To the best of our knowledge, this is the first case report of administration of pregabalin as an adjunctive treatment to a SRI-antipsychotic combination in OCD refractory to stan- dard pharmacotherapy. Pregabalin, a newer antiepileptic drug, binds to the α 2δ subunits of voltage-dependent calcium channels, blocking the calcium influx in presynaptic excita- tory neurotransmitters such as glutamate, thus dampening excitatory neurotransmission in various brain systems. This mechanism of action accounts for the well-established anti- epileptic and antianxiety effects of pregabalin. 5 With respect to pregabalin's specifically anti-OCD mechanism of action, we should note that increased glutamatergic neurotrans- mission is hypothesized to underlie the increased activity of the cortico-striato-thalamic system, which presumably constitutes the core pathophysiologic mechanism of OCD symptoms. 6