Parkinson's disease: low-dose haloperidol increases dopamine receptor sensitivity and clinical response.

Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson's disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson's disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson's disease) was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson's disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects.

Depression treatment by withdrawal of short-term low-dose antipsychotic, a proof-of-concept randomized double-blind study.

BACKGROUND AND OBJECTIVE: Because increased dopamine neurotransmission occurs with most antidepressants, and because antipsychotics cause behavioural supersensitivity to dopamine, short-term low-dose antipsychotic treatment was tested on depressed patients with an expectation of clinical improvement in the supersensitive phase following drug withdrawal. METHOD: This was a randomized, double-blind, placebo-controlled study of 48 patients who met criteria for DSM-IV(®) Major Depressive Disorder, were in a Major Depressive Episode, and had a Hamilton Depression Rating Scale (HAMD) rating of ≥14. Half the participants received 0.25mg oral haloperidol each day for 7 days, after which they received placebo daily for 4 weeks. The other half received placebo throughout the trial. RESULTS: One week after stopping the medication, the HAMD ratings of the drug-treated patients fell by 9.96 points, as compared to a reduction of 8.73 points in the placebo-treated patients, when comparing visits 1 and 4. There was no such difference when comparing visits 2 and 4. The differences were not significant, but indicated a trend. One week after the medication was stopped, the Clinical Global Index fell 1.64±0.18 units for the medication-treated patients, compared to 1.12±0.26 units for the placebo group (P=0.05). The regimen was well tolerated. CONCLUSIONS: Seven days of an ultra-low dose of 0.25mg haloperidol, followed by withdrawal of haloperidol, resulted in clinical depression improvement greater than placebo and significantly decreased psychomotor retardation, consistent with haloperidol-induced behavioural supersensitivity to dopamine. LIMITATIONS: The sample was small. More patients are needed in a future study.