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Pimozide in acute schizophrenia: a pilot study.

Pimozide was used in a pilot study to treat 10 patients with frank symptoms of acute schizophrenia. Eight patients appeared to respond favourably to doses ranging from 12 to 40 mg daily. Two of the patients responded within 1 week and all 8 within 5 weeks. It was possible to discharge all 8 patients from hospital within this time period. It is concluded that oral pimozide is an effective treatment for the whole range of symptoms accompanying acute schizophrenia. Brief representative case histories are presented, and dosage recommendations for the effective treatment of acute schizophrenia with pimozide are discussed.

Acute Disease↗

Pimozide in the maintenance treatment of apathetic and emotionally withdrawn schizophrenics.

An open pilot study was carried out to assess the effectiveness of pimozide as the sole maintenance therapy for chronic institutionalized schizophrenics who were withdrawn and apathetic. A total of 13 patients entered the study and, following withdrawal of all other neuroleptics for 1 month, patients then received pimozide in a dosage increased gradually from 8 mg to 20 mg per day. Patients were assessed using the Brief Psychiatric Rating Scale (BPRS) and the St. Wulston's Ward Behaviour Scale. There was a trend towards improvement when patients were assessed by both rating scales. This was only statistically significant between the pre-pimozide measurement and the 4 and 6-month's assessment on the BPRS. Other differences, including a slight reduction in side-effects, were not statistically significant.

Adult↗

Pimozide as a replacement for maintenance therapy in chronic schizophrenia.

An open 12-week study was carried out to investigate the use of pimozide (12 mg once daily) as a replacement for antipsychotic maintenance therapy in 30 chronic schizophrenics who had responded poorly to previous neuroleptic monotherapy or polytherapy. After 8 weeks of treatment with pimozide, all 18 symptoms of the Brief Psychiatric Rating Scale were improved from previous treatment values. These differences were statistically significant for conceptual disorganization, depressive mood, hostility and motor retardation. Eleven patients who clearly responded well during the trial and consequently continued pimozide monotherapy were judged, 1 year later, to be functioning as well, or better, than with pre-trial drug treatment.

Adult↗

The Scottish First Episode Schizophrenia Study. II. Treatment: pimozide versus flupenthixol. The Scottish Schizophrenia Research Group.

In a randomised double-blind study, 46 first episode schizophrenics were given pimozide or flupenthixol for up to 5 weeks; the mean daily dose at the end was 18.8 mg pimozide and 20 mg flupenthixol. There were no significant between-drug differences in the effect on mental state or behaviour; positive schizophrenic symptoms responded to treatment, negative symptoms did not. Most patients required anti-Parkinsonian medication. Poor response was associated with 'organicity'. A switch to maintenance therapy after 5 weeks, the outcome of successful treatment and patient cooperation, was achieved in only 54%. There was no relationship between plasma prolactin levels and severity of schizophrenic symptoms in unmedicated patients. Pimozide produced greater elevation of plasma prolactin. Plasma neuroleptic levels showed drug compliance was satisfactory throughout in only 54%.

Adolescent↗

Endocrine effects of pimozide, a specific dopaminergic blocker.

Pimozide, a specific blocker of dopaminergic receptors, was administered orally to 10 adult male volumteers for 4 days. Half of the subjects received 4 mg/day and the other half 2 mg/day. Blood samples were obtained the day before, the 4th day of Pimozide, and 4 days after the last dose of the drug for the determination of LH, FSH, GH, PRL, TSH, cortisol and testosterone levels. Twenty-four h urinary collections were obtained for the determination of LH and FSH levels. Plasma LH levels decreased and plasma PRL levels increased in the combined groups during Pimozide. Plasma TSH levels decreased during treatment in the 4 mg group only. Urinary LH and plasma testosterone levels decreased in the post-treatment period in the combined groups. These data support the concept of a dopaminergic control of the secretion of several hormones in the human.

Adult↗

Short-term versus longer term pimozide therapy in Tourette's syndrome: a preliminary study.

The authors randomized 10 patients (age range, 7 to 13 years) with Tourette's syndrome who had achieved a stable level of tic control on open-label pimozide to continue on pimozide (n = 6) or be withdrawn from therapy (n = 4) in a double-blind study. The median time to end point (the time when an increased dose of study medication was required to control tics) was 231 days (continued) versus 37 days (withdrawn), and the survival curves were significantly different (p = 0.02). Chronic, longer term treatment with pimozide appears to be more effective in controlling the course of tics than using the drug acutely to treat an exacerbation.

Adolescent↗

A parametric evaluation of the hedonic and motoric effects of drugs: pimozide and amphetamine.

This study uses a curve-fitting approach to evaluate the effects of drugs on reinforced responding in rats. The subjects obtained reinforcement according to a series of five different variable-interval schedules (a five-component multiple schedule). For each rat, pimozide, a neuroleptic, decreased response rate, and the decrease was associated with (1) a decrease in the estimated asymptotic response rate and (2) an increase in the rate of reinforcement necessary for half-asymptotic responding. That is, pimozide decreased the proportion of responding maintained by a given rate of reinforcement. In contrast, intermediate doses of amphetamine increased response rate and increased the proportion of responding maintained by a given rate of reinforcement. It was proposed that the response rate asymptote indexes motor capacity, and the rate of reinforcement necessary for half-asymptotic responding indexes reinforcement efficacy; accordingly, pimozide decreased motor capacity and reinforcement strength and amphetamine increased reinforcement strength.

Animals↗

Comparison of chlorpromazine, haloperidol and pimozide in the treatment of phencyclidine psychosis: DA-2 receptor specificity.

Three neuroleptics were used to treat phencyclidine (PCP) psychosis. These included chlorpromazine, a DA-1 and DA-2 dopamine antagonist with noradrenergic effects; haloperidol, a predominantly DA-2 antagonist with noradrenergic effects; and pimozide a predominantly DA-2 antagonist with no noradrenergic activity. Three cohorts of randomly selected young white adult males were studied. Responses to haloperidol and pimozide were statistically equivalent and both were significantly superior to chlorpromazine. These results further support the role of the DA-2 receptor in PCP psychosis and tend to rule out a noradrenergic role. The authors therefore suggest that DA-2 blockers, such as haloperidol or pimozide be employed as treatment of choice in PCP psychosis.

Adult↗

Effects of lithium and rubidium on antinociception and behaviour in mice. II. Studies on three tricyclic antidepressants and pimozide.

The effects of LiCl and RbCl on the antinociception caused by three antidepressants and pimozide were studied in mice. On the hot plate LiCl given acutely or chronically did not modify the antinociception of any drug although it augmented hypothermia induced by chlorimipramine and occasionally also that caused by desipramine and doxepine, and also caused definitive changes in motor abilities. RbCl given acutely (2.5 mEq/kg) or for 5 or 21 days in tap water (1 g/liter) abolished the antinociception caused by pimozide and when given acutely or for 5 days that of desipramine. In the phenylquinone writhing test LiCl when given for 21 days enhanced the nearly complete antinociception caused by chlorimipramine, doxepine and pimozide. These effects of ions did not seem to be related to changes in body temperature, motor coordination nor motility.

Animals↗

Pimozide: use in dermatology.

Pimozide is widely used in psychiatry for chronic psychoses, schizophrenia, the syndrome of Gilles de la Tourette and to a certain extent, also in dermatology. The only dermatological indication is for delusions of parasitosis. Though there is a good rationale for using pimozide in this disease, the majority of the studies on pimozide in dermatology are uncontrolled trials and case reports.

Antipsychotic Agents↗

Low-dose pimozide augmentation of serotonin reuptake blockers in the treatment of trichotillomania.

BACKGROUND: There is some overlap in the phenomenology and treatment response of trichotillomania, Gilles de la Tourette's syndrome (TS), and obsessive compulsive disorder (OCD). Neuroleptics may play a role in the treatment of TS as well as refractory OCD, and the question arises whether this also holds for trichotillomania. METHOD: Patients with trichotillomania were treated in open clinical practice with serotonin reuptake blockers. When symptom resolution was incomplete or symptom relapse occurred, low-dose pimozide was added. RESULTS: In six out of seven patients, the addition of pimozide to a serotonin reuptake blocker led to an improvement in hair pulling. In patients who were able to tolerate their medication, this response was sustained. CONCLUSION: Augmentation of serotonergic agents with dopamine blockers may play a role in the treatment of trichotillomania. Further controlled trials of pimozide augmentation in trichotillomania are needed.

Adult↗

Dissociation of the attentional and motivational effects of pimozide on the threshold for rewarding brain stimulation.

The decreased sensitivity of animals to rewarding brain stimulation caused by pimozide has been interpreted as a selective pharmacologic blockade of central reward pathways rather than a nonspecific disruption of performance. In an attempt to confirm this hypothesis, the effects of pimozide on both reward and detection thresholds for intracranial stimulation delivered to the medial forebrain bundle-lateral hypothalamic area (MFB-LH) were determined in four animals. The drug caused a systematic increase in the reward threshold of each subject but had no such effect on the detection threshold. We conclude that pimozide selectively inhibits the rewarding effects of brain stimulation, and that therefore, the D2 dopamine receptor has a major role in activating central reward pathways subserving pharmacologic and electrical reinforcement. The dual anhedonic/antipsychotic effects of neuroleptic medication are discussed as a possible paradox of central importance to the psychopathology of schizophrenia.

Animals↗

Delusions of infestation treated with pimozide: a follow-up study.

Fourteen patients with monosymptomatic delusions of infestation were followed-up 19-48 months after treatment with pimozide was terminated. Seven patients had remained in remission since the treatment. Three had developed relapses, but were without symptoms with intermittent treatment. Four patients responded poorly to pimozide and had still symptoms at the follow-up. The study indicates, that a large proportion of patients with monosymptomatic delusions of infestation treated with pimozide will be able to discontinue the medication for years without recurrence of their delusions.

Aged↗

Effect of nitrendipine, diltiazem, trifluoperazine and pimozide on serotonin2 (5-HT2) receptor activation in the rat uterus and jugular vein.

The present study explored the calcium source used in serotonin (5-HT)-induced contractions mediated by 5-HT2 receptor activation in the rat uterus and jugular vein in vitro. In the rat uterus, the calcium channel antagonists, nitrendipine and diltiazem, and the neuroleptic agents, trifluoperazine (TFP) and pimozide, antagonized potently and noncompetitively 5-HT-induced contractions. These data are compatible with the contention that 5-HT-induced contractions in uterine smooth muscle require extracellular sources of calcium. In contrast, neither diltiazem nor nitrendipine inhibited the contractile response to 5-HT in the rat jugular vein although 5-HT-induced contractions in the jugular vein required the presence of extracellular calcium. This difference in sensitivity to calcium channel antagonists between the uterus and jugular vein was not related to differences in the receptor occupancy-response curves for 5-HT as these were similar in the rat uterus and jugular vein. Furthermore, in the jugular vein, neither diltiazem nor nitrendipine were markedly effective in blocking contractions produced by potassium chloride, an agent that activates voltage-dependent calcium channels, suggesting that this tissue lacks calcium channels susceptible to blockade by conventional calcium channel antagonists. Although responses to 5-HT in the jugular vein were only affected marginally by calcium channel antagonists, TFP and pimozide produced concentration-dependent rightward parallel shifts of 5-HT-induced contractions in the jugular vein. Furthermore, both TFP and pimozide showed high affinity at 5-HT2 binding sites in rat brain cortical membranes and the apparent dissociation constant at 5-HT2 receptors in the jugular vein was 38 and 31 nM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pimozide treatment of the negative schizophrenic syndrome: an open trial.

Reports over the last 20 years suggest that pimozide, a neuroleptic of the diphenylbutylpiperidine (DPBP) group, might be helpful in the treatment of negative symptoms of schizophrenia, which are considered less responsive to standard neuroleptics than are positive symptoms. Research suggests that neuroleptic drugs of the DPBP group possess a unique property--potent calcium channel antagonism--which could explain their ability to relieve negative symptoms. Earlier reports, however, used measures not specifically designed to assess the negative syndrome. The Positive and Negative Syndrome Scale (PANSS) was developed and standardized to measure the negative syndrome in schizophrenia. The authors used the PANSS to study the effects of pimozide in a 6-week, open clinical trial with 10 neuroleptic-resistant schizophrenic inpatients who had prominent deficit features. Negative but not positive symptoms improved significantly, suggesting that the drug might target the negative profile. The authors discuss possible pharmacologic mechanisms for pimozide's potentially distinct clinical properties.

Adult↗

Pimozide in the treatment of some "social maladjustments" in "personality disorders".

Forty patients with some "social maladjustments" or disturbed interpersonal relationship under 2 mg pimozide (Orap: a 24 h long-acting neuroleptic) for six to twelve months. Concomitant but complementary medication was kept unchanged. Control was based on: long-term investigation (1/2 - 1 year), quantification, use of two scales. Statistical evaluation of the changes in "cardinal symptoms" showed a significant improvement in tension, disorders of sleep, intellectual disturbances, cardiovascular symptoms and gastrointestinal complaints. More detailed analysis of the other 27-item rating scale revealed a dramatic improvement in anxiety and paranoidism. The overall appreciation shows that: 25 patients responded well or very well to pimozide, eight did moderately, seven poorly. Neurasthenia and related states with predominant asthenia turned out to be no indication for pimozide treatment. Except for some cases of increased fatigue, tolerance was exceptionally good. The trial showed that extra patience is required from the therapist as a clinical onset of one to two months is not uncommon.

Adult↗

Delusions of infestation treated by pimozide: a double-blind crossover clinical study.

Eleven patients with delusions of infestation were treated with pimozide using a double-blind crossover technique. Ten out of 11 patients improved. The investigation showed significant relief of itch and delusions during pimozide treatment. Brief Psychiatric Rating Scale (BPRS) points decreased significantly. Adverse effects were few by 2 patients showed dose-related depressive reactions during treatment. Pimozide treatment of patients with delusions of infestation should be entrusted to dermatologists, because these patients with delusions differ from most patients attending psychiatric clinics in that they have a monosymptomatic hypochondriacal psychosis.

Acari↗

Modification by sulpiride, pimozide, or domperidone of apomorphine's effects on learning in hypoxic rats.

The study of apomorphine's interaction with three dopaminergic antagonists (domperidone, sulpiride and pimozide) is an attempt to characterize the dopaminergic receptors involved in the dopaminergic agonist-induced protection against hypobaric hypoxia. Apomorphine (1 mg X kg-1 but not 0.01 mg X kg-1) reduced total performance (avoidance + escape responses); this effect was antagonised by domperidone and pimozide--not by sulpiride--and appeared to have a peripheral origin. Apomorphine (0.01 and 1 mg X kg-1) increased the avoidance performance during hypoxia. This antihypoxic protection was not suppressed by domperidone, confirming its central origin, but was antagonised both by sulpiride and pimozide. The receptors involved in the anti-hypoxic protective effect appear therefore to be cerebral D4 receptors, according to the classification of Seeman.

Animals↗