Objective: The study aimed to assess the antidepressant efficacy and tolerability of adjunctive ropinirole in outpatients with treatment-resistant depression (TRD).
Method: The study sample consisted of patients with a major depressive episode (diagnosed according to DSM-IV criteria) and TRD. Ropinirole 0.25 to 1.5 mg daily was added to tricyclic antidepressants or selective serotonin reuptake inhibitors. We conducted assessments at baseline and at weeks 2, 4, 8, 12, and 16. We defined response as a 50% or greater reduction of the Montgomery-Asberg Depression Rating Scale (MADRS) total score plus a score of 1 ("very much improved") or 2 ("much improved") on the Clinical Global Impression of Improvement scale at endpoint. Tolerability was monitored with the Dosage Record Treatment Emergent Symptom Scale.
Results: Seven patients had major depressive disorder, and 3 had bipolar II disorder. The mean maximum dose of ropinirole was 1.33 mg daily. Mean (SD) scores on the MADRS decreased from 29.6 (7.6) at baseline to 16.9 (12.1) at endpoint (P < 0.02). At endpoint, 4 of 10 (40%) patients were responders. Two patients discontinued ropinirole because of dizziness.
Conclusions: These pilot data suggest that, in selected cases of TRD, ropinirole augmentation of antidepressants is effective and relatively well tolerated.
(Can J Psychiatry 2005;50:357-360)
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* This is a novel potential treatment strategy for resistant depression.
* The study has high ecologic validity because the sample of depression patients was heterogeneous.
* Adding ropinirole to antidepressant therapy is safe in the treatment of depression.
* The study population was heterogeneous.
* The sample size was small.
* This is an uncontrolled experimental study.
Key Words: resistant depression, dopamine agonists, augmentation therapy
Ropinirole is a nonergoline dopaminc D^sub 2^-D^sub 3^ receptor agonist indicated for treating Parkinson's disease. The drug is inactivated by cytochrome P450 isoenzyme CYP1A2 in the liver, and its half-life is approximately 6 hours (1). Laboratory (2) and clinical studies (3-9) support the hypothesis of an anti-depressant effect exerted by pramipexole, a dopamine D^sub 2^-D^sub 3^ receptor agonist. We conducted a pilot, prospective, open study of the efficacy and tolerability of ropinirole augmentation in patients with treatment-resistant depression (TRD).
Materials and Methods
The study was a 16-week, prospective, open trial conducted at the Department of Psychiatry of the University of Pisa among patients with TRD. The site of this trial is a national referring center for mood and anxiety disorders. Adult patients (aged over 18 and under 75 years) diagnosed with a major depressive episode according to DSM-IV criteria were referred to our clinic during a 3-month period and were consecutively assessed for eligibility for study entry. We included in the study patients who did not respond to at least one antidepressant treatment; this was characterized by adequate dosages and an extended period of administration (for example, sertraline 100 mg daily for 6 weeks) (10). Treatment was constant for at least 6 weeks prior to ropinirole augmentation. Table 1 reports concomitant treatments, as well as their dosage and duration prior to ropinirole add-on. We assessed patient adherence and resistance to prior antidepressant treatments prospectively in clinical interviews of both patients and relatives. We excluded patients with physical diseases that might interfere with the conduct of the study, as well as those with substance abuse, serious suicide risk, and psychotic symptoms. Blood pressure was measured at baseline, and routine blood tests performed within the 3 months prior to enrolment were screened to rule out untreated concomitant physical illnesses. …