A 2022 case report describes a 51-year-old woman with bipolar I disorder and obsessive compulsive disorder receiving long-term antipsychotics and valproate who developed parkinsonian symptoms during admission for bipolar depression. Neurologic evaluation including a negative DaTSCAN supported a pharmacologic cause. Lurasidone was discontinued and pramipexole was initiated. Improvement in parkinsonian symptoms and remission of depressive symptoms were observed. The authors note that while guidelines recommend discontinuing or switching the causative agent, this may not always be feasible in complex psychiatric cases, and suggest pramipexole may be considered in the management of drug induced parkinsonism, particularly in patients with comorbid depressive disorders, while acknowledging that further research is needed. Of note, the antipsychotic was discontinued before pramipexole was initiated in this case, making it uncertain whether combination use would produce the same extent of effect. [1]
A 2012 randomized, double-blind, placebo-controlled pilot trial evaluated adjunctive pramipexole in 24 adults (43.3 ± 12.2 years) with DSM-IV schizophrenia or schizoaffective disorder receiving stable second-generation antipsychotics at ≥240 mg/day chlorpromazine equivalents, including risperidone, olanzapine, quetiapine, clozapine, and ziprasidone. Pramipexole, a preferential dopamine D3 agonist with D2 activity, was titrated over 6 weeks to a mean final dose of 4.25 ± 0.38 mg/day and continued for up to 12 weeks while background antipsychotic therapy was maintained. Adjunctive pramipexole was associated with greater reductions in Positive and Negative Symptom Scale (PANSS) total scores compared with placebo (−10.2% vs −4.9%, p= 0.044) and greater improvement in PANSS positive symptoms (−19.0% vs +7.2%, p= 0.006). Changes in negative symptoms were not statistically significant. Extrapyramidal symptoms (EPS) were assessed using the Simpson–Angus, Barnes Akathisia, and Abnormal Involuntary Movements (AIMS) scales; baseline scores were low, and no significant between-group differences were observed. The authors noted limited statistical power to detect differences in extrapyramidal or mood symptoms. Adverse effects included disorganized thinking, erectile dysfunction, increased auditory hallucinations, dizziness, and modest weight gain in a minority of patients. [2]
Additional studies have evaluated adjunctive pramipexole in patients with schizophrenia receiving ongoing antipsychotic therapy. In a 1997 open-label trial (n= 15), pramipexole was added to stable haloperidol (oral 5 to 20 mg/day or depot formulations) and titrated up to 10.25 mg/day over 2 weeks, with maintenance through day 28. Nine of 15 patients achieved >20% reduction in PANSS total score (22% to 62% reduction). Three patients discontinued due to worsening positive symptoms. Insomnia was the most frequent adverse effect (4 patients). EPS were assessed using the Simpson–Angus and Hillside Akathisia scales; no worsening from baseline was observed, and no clinically relevant cardiovascular, electrocardiographic, or laboratory abnormalities were reported. In a separate 16-week randomized, double-blind, placebo-controlled trial (n= 200), pramipexole 0.75 mg twice daily was added to stable antipsychotic regimens in patients with schizophrenia or schizoaffective disorder. Compared with placebo, pramipexole did not produce significant differences in PANSS total, positive, negative, or general psychopathology scores at weeks 8 or 16, and no significant differences were observed in Clinical Global Impressions–Severity of Illness scale (CGI-S) or cognitive outcomes. Extrapyramidal effects were infrequent in both groups, with no significant between-group differences on Simpson–Angus ratings. Of note, cariprazine was not among the antipsychotics included in this trial. Collectively, these studies describe pramipexole administered concomitantly with antipsychotics, with variable effects on symptom outcomes and no clear evidence of exacerbation of extrapyramidal or other dopaminergic adverse effects within the small samples and short duration studied. [3], [4]