Neuroleptic Discontinuation Research Articles

Subjective discomfort and lack of volitional drive with neuroleptic pharmacotherapy - a phenomenological case study

IntroductionIn comparison to extrapyramidal and metabolic side effects, the subjective aspects of neuroleptic treatment have been less extensively researched. Nevertheless, they are equally significant given their potential to influence adherence and functional outcome. Historically, terms such as “neuroleptic dysphoria,” “neuroleptic-induced psychic indifference,” and “neuroleptic-induced deficit syndrome” were used to characterize a range of unpleasant mood states on the one hand and a documented and observable motivational deficit on the other. The latter aligns with the findings from preclinical neuroscientific studies and animal models highlighting the significant involvement of mesolimbic dopamine in motivational processes. Despite an abundance of anecdotal data these adverse effects are often undetectable in large-scale clinical studies that utilize standardized assessment measures.ObjectivesTo present adverse subjective changes in arousal, mood and volitional drive resulting from neuroleptic intake from a patient’s perspective.MethodsThe subject is a patient, with no reported negative symptoms or lasting functional impairment described, who underwent a gradual 6-month discontinuation of risperidone in an outpatient setting following a complete recovery after a single psychotic episode. A semi-structured interview modelled after The Clinical Assessment Interview for Negative Symptoms (CAINS) was conducted. We aimed to elicit descriptions of the subjective experience while ensuring our approach remained non-suggestive.ResultsIn addition to describing potential akathisia and lethargy at higher doses, the subject reported a significant lack of motivation and a notably reduced willingness to exert effort towards achieving specific goals or engaging in activities that he still found rewarding or pleasurable. Furthermore, he consistently noted gradual improvements across various psycho-social aspects following the discontinuation of the medication. These adverse and unpleasant experiences were presented as the primary reason for wanting to discontinue pharmacological treatment.ConclusionsCertain adverse effects of antipsychotic medications can only be elucidated by the clinician through the examination of the patient’s subjective experiences. Medication induced dysphoria and volitional deficits have the potential to profoundly impact treatment adherence, leading to unrecommended discontinuation of neuroleptics, and can cause important functional impairment.Disclosure of InterestNone Declared

Neuroleptic Malignant Syndrome or Catatonia? A Case Report

IntroductionA review of the literature has shown that there are many similarities in the presentation of neuroleptic malignant syndrome (NMS) and catatonia. Attempts to reconcile the differences have been made by suggesting that NMS and catatonia may represent different presentations of the same illness or that they lie within the same spectrum of a poorly understood clinical syndrome. The described case is of a patient who presented with NMS and catatonia which was difficult to diagnose, but which responded to treatment with intravenous diazepam.Case presentationThe case concerns a 22-year-old male admitted for pulmonary hypertension to an intensive care unit (ICU). Three days following admission, he developed a high fever that did not respond to antibiotics. The patient then developed rigidity, nocturnal agitation, decreased responsiveness, and somnolence. Without the use of bromocriptine (Novartis, Basel, Switzerland) or dantrolene (Par Pharmaceuticals, Chestnut Ridge, USA) discontinuation of neuroleptics combined with intravenous diazepam (Pfizer, NY, USA) led to a very rapid response and marked improvement in the case.ConclusionsEarly recognition and management of NMS and MC in a complex, gravely ill patient, may be accomplished in the ICU despite obfuscation of traditional signs and symptoms of the NMS and MC syndrome. Such interventions can have life-saving effects on patients in danger of fatal autonomic instability.

Clinician perspectives on supporting adults with psychosis who wish to discontinue neuroleptic medication: qualitative analysis

ABSTRACTPurpose: Research consistently demonstrates that service-users perceive limited choice in whether neuroleptic medication should be dis- continued. Clinicians identify barriers to making shared decisions around medication; however, little is known about how clinical decisions are made regarding whether to support service-users in discontinuing neuroleptic medication. This study examined clinicians’ perspectives on supporting adults who wish to discontinue neuroleptic medication.Materials and Methods: Grounded theory was used to investigate the views and perspectives of clinicians by individual in-depth interviews.Results and Conclusions: A theoretical model (Figure 1) was developed depicting a complex process of decision-making for clinicians working with service-users wishing to discontinue neuroleptics. Decision-making was influenced by clinicians’ personal and professional experiences, and underpinned by their assessment of risk factors and anticipated prognoses for service- users wishing to discontinue neuroleptics. This determined whether clinicians adopted a collaborative or coercive communication style with service-users. Decisions to support discontinuation elicited a range of anxieties in clinicians, leading to actions focused on harm reduction. Decisions about neuroleptic discontinuation are subjective and dependent on clinicians’ previous experiences and judgements regarding potential risk factors. The development of national guidelines, training, resources and support services are required for clinicians to be able to effectively support service-users to discontinue neuroleptic medication.

Possible Paliperidone-Induced Neuroleptic Malignant Syndrome: A Case Report

Possible Paliperidone-Induced Neuroleptic Malignant Syndrome: A Case Report

Tardive parkinsonism in a bipolar patient: Post-mortem examination supports a physiological rather than pathological dysfunction

We describe a case of tardive parkinsonism in the setting of bipolar syndrome, and we offer pathological confirmation that idiopathic Parkinson disease was not the underlying etiology. A 74-year-old Hispanic woman with a history of bipolar disease was noted to have oro-buccal-lingual chorea and parkinsonian symptoms such as resting tremor, rigidity, bradykinesia, and gait disorder persisting several months after neuroleptic discontinuation. She had minor improvement in ambulation with levodopa treatment, and she significantly improved in ambulation only during her manic states. Examination of the subject's post-mortem brain revealed no explicit evidence of degeneration in substantia nigra or other brainstem centers, and no nigral or cortical Lewy bodies were present. Glial cytoplasmic inclusions (characteristic of multiple systems atrophy) and globose neurofibrillary tangles (seen in progressive supranuclear palsy) were not seen either. This patient's presentation was most consistent with neuroleptic-induced parkinsonism and tardive dyskinesia; the etiology was likely related to previous neuroleptic exposure.

Neuroleptic discontinuation during dementia care: a recent trial and its implications for practice

Neuroleptic discontinuation during dementia care: a recent trial and its implications for practice

Olanzapine-Induced Tardive Dystonia Successfully Treated by Tetrabenazine

Back to table of contents Previous article Next article LETTERFull AccessOlanzapine-Induced Tardive Dystonia Successfully Treated by TetrabenazineBoris Rauchverger M.D.,Victoria Isakov M.D.,Mahmoud Jabarin M.D.,Boris Rauchverger M.D.Search for more papers by this author,Victoria Isakov M.D.Search for more papers by this author,Mahmoud Jabarin M.D.Search for more papers by this author,Published Online:1 Oct 2007AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: Tardive dystonia (TD) is one of the tardive syndromes, along with tardive dyskinesia, and tardive akathisia. It is an adverse effect [BR2] usually associated with conventional antipsychotics, though it has also been observed in patients treated with atypical antipsychotics, particularly olanzapine. 1 , 2 Tardive dyskinesia is uncommon, severe, and debilitating, 3 rarely remits completely and has no proven remedy. 4 Dopamine-depleting agents, such as tetrabenazine, have shown a beneficial effect on TD, 5 but efficacy has yet to be proven. We present an unusual case of TD that emerged after 5 years of olanzapine monotherapy, and did not remit 1 month after olanzapine discontinuation, but successfully resolved following initiation of tetrabenazine therapy. Mr. M, 47-years-old, diagnosed with chronic schizophrenia, had an unremarkable medical past, and no family history of movement disorders. Since the year 2000, M. was treated with olanzapine (5 mg/day) monotherapy, with no adverse effects. His condition was described as partial remission with stable deficit. During February 2006 he began complaining about periodic involuntary continuous painful muscle spasms in the neck, which lasted a few minutes. Within 3 months symptoms increased in length, severity and frequency. Moreover, the chest and upper abdomen were also involved in involuntary contractions causing heavy breathing and eating difficulties and repeated vomiting. Each respiration was accompanied by unilateral neck spasms, cramps, leading to regurgitation and difficulty in breathing. He tried to support himself to prevent muscle contractions, but without success. M. became afraid and distressed. He was referred to a general hospital and underwent comprehensive medical and neurological examinations. Somatic pathology was excluded. His laboratory tests (blood oxygenation, CBC, thyroid hormones, electrolytes, magnesium, calcium, copper, liver enzymes) and brain CT scan were normal and he was eventually diagnosed with drug-induced tardive dystonia. Olanzapine was stopped in June 2006 but the tardive dystonia continued. Adjunctive clonazepam (2 mg/day) was not beneficial. One month later, tetrabenazine (25 mg/day) was initiated, and gradually uptitrated to 75 mg/day. During the second week of treatment his condition improved and within 4 weeks almost all involuntary movements remitted. Quetiapine 100 mg/day was started in August 2006 with adjunct tetrabenazine, and he remains free of involuntary movements. Tardive dystonia is a late-onset side effect of antipsychotic treatment, with persistent dystonic movements of focal onset involving mainly the craniocervical region. In our case, the dystonia appeared after 5 years of olanzapine treatment, was multifocal including the neck, chest and upper abdomen, accompanied by labored breathing and eating disturbances. Its unusual presentation made diagnosis difficult. Commonly proposed treatment interventions such, as neuroleptic discontinuation and benzodiazepines were ineffective. Paleacu et al. 5 reported moderate effect of tetrabenazine on movement disorders. We observed a pronounced and quick effect of tetrabenazine on distressing, and severely debilitating TD. Further study is warranted to confirm the efficacy of tetrabenazine in intractable cases of TD. Sha’ar Menashe Mental Health Center, Hadera, IsraelSha’ar Menashe Mental Health Center, Hadera, IsraelSha’ar Menashe Mental Health Center, Hadera, IsraelReferences1 . Gunal DI, Onultan O, Afsar N, et al: Tardive dystonia associated with olanzapine therapy. Neurol Sci 2001; 22:331–332Google Scholar2 . Charfi F, Cohen D, Houeto JL, et al: Tardive dystonia induced by atypical neuroleptics: a case report with olanzapine. J Child Adolesc Psychopharmacol 2004; 14:149–152Google Scholar3 . Wojcik JD, Falk WE, Fink JS, et al: A review of 32 cases of tardive dystonia. Am J Psychiatry 1991; 148:1055–1059Google Scholar4 . Papapetropoulos S, Wheeler S, Singer C: Tardive dystonia associated with ziprasidone. Am J Psychiatry 2005; 162:2191Google Scholar5 . Paleacu D, Giladi N, Moore O, et al: Tetrabenazine treatment in movement disorders. Clin Neuropharmacol 2004; 27:230–233Google Scholar FiguresReferencesCited byDetailsCited byValbenazine as the first and only approved treatment for adults with tardive dyskinesia23 January 2018 | Expert Review of Clinical Pharmacology, Vol. 11, No. 3Calcium channel blockers for antipsychotic-induced tardive dyskinesia26 March 2018 | Cochrane Database of Systematic Reviews, Vol. 2018, No. 3Neurochemical Research, Vol. 41, No. 9Paediatrics & Child Health, Vol. 17, No. suppl_BTetrabenazine for the Treatment of Tardive Dyskinesia20 April 2011 | Annals of Pharmacotherapy, Vol. 45, No. 4Cochrane Database of Systematic ReviewsPaediatrics & Child Health, Vol. 16, No. 9Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology, Vol. 20, No. 3Expert Opinion on Pharmacotherapy, Vol. 10, No. 17Transient Tardive Dystonia: Overview and Case PresentationJournal of Psychiatric Practice, Vol. 14, No. 4Pharmacoepidemiology and Drug Safety, Vol. 17, No. 6 Volume 19Issue 4 Fall, 2007Pages 484-485 Metrics PDF download History Published online 1 October 2007 Published in print 1 October 2007

Possible Neuroleptic Malignant Syndrome Associated With Paliperidone

Possible Neuroleptic Malignant Syndrome Associated With Paliperidone

Olanzapine-Induced Tardive Dystonia Successfully Treated by Tetrabenazine

Olanzapine-Induced Tardive Dystonia Successfully Treated by Tetrabenazine

Dementia with Lewy Bodies: Therapeutic Opportunities and Pitfalls

To review diagnoses and challenges of treating patients with dementia with Lewy bodies (DLB), commonly considered the second most common form of dementia. MEDLINE, Web of Science, and International Pharmaceutical Abstracts databases were searched in January 2006 for clinical studies, case series, case studies, letters, and review articles on the treatment of DLB. Search terms included: aripiprazole, cholinesterase inhibitors, clozapine, dementia with Lewy bodies, donepezil, galantamine, Lewy body dementia, neuroleptics, olanzapine, quetiapine, risperidone, rivastigmine, tacrine, ziprasidone. Applicable articles in the English language were reviewed. The bibliographies of these articles provided additional references. Articles describing studies, case series, and case studies are included in this review. DLB is commonly considered the second most common form of dementia, although some experts believe vascular dementia to be the second most common form. DLB is often under-diagnosed and misdiagnosed as Alzheimer's disease or Parkinson's related dementia. The core features of dementia with Lewy bodies are cognitive decline plus at least one of the following: fluctuations in cognition, visual hallucinations, and parkinsonism. Other supportive features include: neuroleptic sensitivity, repeated falls, syncope, transient loss of consciousness, REM sleep disturbances, depression, delusions, and nonvisual hallucinations. Increased prudence with the use of neuroleptic agents is essential in DLBs because the use of these agents is associated with physical and cognitive decline and increased mortality. While neuroleptic sensitivity has been reported with the use of both typical and atypical antipsychotic medications, these medications are often necessary for the treatment of psychotic symptoms. Decreases in neuroleptic sensitivity can often be achieved by dose reductions, although neuroleptic discontinuation is sometimes necessary. Cholinesterase inhibitors may be especially useful in the treatment of DLB. Cholinergic deficits are associated with visual hallucinations, and cholinesterase inhibitors often result in resolution of hallucinations, improved cognition, and decreased behavioral disturbances.

Can Medication-Free Research Ever Be Ethical in Older People With Psychotic Disorders?

Can Medication-Free Research Ever Be Ethical in Older People With Psychotic Disorders?

Neuroleptic malignant syndrome induced by atypical neuroleptics and responsive to lorazepam

The authors report three cases of neuroleptic malignant syndrome (NMS) induced by atypical antipsychotics (olanzapine and clozapine) which showed classic features of NMS including muscular rigidity and prominent fever. Case reports. A 66-year-old man with dementia and alcohol abuse developed NMS while on olanzapine for agitation and combativeness. A 62-year-old man with schizophrenia developed NMS 6 days after starting clozapine. A 43-year-old man with bipolar disorder developed NMS 14 days after starting clozapine. All three cases showed classic features of NMS including muscular rigidity and fever. Resolution of fever and muscular rigidity occurred within 72 hours with discontinuation of neuroleptics, supportive care, and lorazepam. The NMS rating scale reflected daily clinical improvement. Classic NMS characterized by muscular rigidity and prominent fever may occur with atypical neuroleptics. Our cases suggest recovery from NMS associated with atypical neuroleptics may be hastened by lorazepam, as was previously reported for NMS from typical neuroleptics. Also, the NMS rating scale was sensitive to clinical improvement.

Clinical Outcome Following Neuroleptic Discontinuation in Patients With Remitted Recent-Onset Schizophrenia

Objective: The goal of this report was to examine the clinical course following neuroleptic discontinuation of patients with recent-onset schizophrenia who had been receiving maintenance antipsychotic treatment for at least 1 year. Method: Fifty-three volunteer patients with recent-onset schizophrenia who had been clinically stabilized on a maintenance regimen of fluphenazine decanoate for a mean of 16.7 months had their antipsychotic medications withdrawn under clinical supervision. Participants initially entered a 24-week, double-blind crossover trial in which fluphenazine and placebo were administered for 12 weeks each. For those who did not experience symptom exacerbation or relapse during this period, fluphenazine was openly withdrawn; participants were then followed for up to 18 additional months. Results: When a low threshold for defining symptom reemergence was used, 78% (N=39 of 50) of the patients experienced an exacerbation or relapse within 1 year; 96% (N=48 of 50) did so within 2 years. Mean time to exacerbation or relapse was 235 days. When hospitalization was used as a relapse criterion, only six of 45 of individuals (13%) experiencing an exacerbation or relapse who continued in treatment in the clinic were hospitalized, demonstrating the sensitivity of the psychotic exacerbation criterion. Conclusions: The vast majority of clinically stable individuals with recent-onset schizophrenia will experience an exacerbation or relapse after antipsychotic discontinuation, even after more than a year of maintenance medication. However, clinical monitoring and a low threshold for reinstating medications can prevent hospitalization for the majority of these patients.

The natural history of tardive dystonia. A long-term follow-up study of 107 cases.

The clinical picture, risk factors and natural history of tardive dystonia resulting from dopamine-receptor antagonist (DRA) treatment in 107 patients (57 male and 50 female), seen between 1972 and 1995, are described. The mean age at onset (+/- SD) was 38.3 +/- 13.7 years (range 13-68 years), and the age at last follow-up was 46.3 +/- 15.7 years (range 15-80 years). These patients had received DRAs for schizophrenia (39%), for other psychiatric conditions (51.5%) and for non-psychiatric disorders (9.5%). All classes of neuroleptics used were implicated in producing tardive dystonia, which was found to develop at any time, ranging from 4 days to 23 years after their introduction (median 5, mean 6.2 +/- 5.1 years); there was no 'safe' period. Men were significantly younger than women at onset of dystonia, which developed after shorter exposure in men. At onset, the dystonia was focal in 83% of cases, but progressed over months or years and remained focal in only 17% at the time of maximum severity. The craniocervical region was involved in 87% of cases, and was the most commonly affected site both at onset and at maximum severity. There was a correlation between the site and age of onset; the site of onset ascended from the lower limbs to the face as the mean age of onset increased. Overall, the phenomenology of tardive dystonia was indistinguishable from that of primary (idiopathic) dystonia, although retrocollis and anterocollis, as well as torticollis to the right, were significantly more common in tardive dystonia. It is a very persistent disorder; only 14% of our patients had a remission over a mean follow-up period of 8.5 years. Remission occurred after a mean of 5.2 years from onset (range 1-12 years) and 2.6 years after discontinuation of neuroleptics (range 1 month to 9 years). Discontinuation of neuroleptics increased the chances of remission fourfold. Patients with < or = 10 years on neuroleptics had a five times greater chance of remission than those with > 10 years exposure, suggesting that the pathogenetic changes in tardive dystonia may become irreversible after long-term use of these drugs. None of the numerous treatments tried in these patients, including clozapine and botulinum toxin injections, seemed to relate to overall outcome, but there was a significant negative association between the occurrence of remission and the use of benzodiazepines. Although there were hints of a possible genetic predisposition, the question as to whether patients with tardive dystonia have an underlying vulnerability remains unanswered.

急激な向精神病薬，抗うつ病薬の中断によって発症した非定型的悪性症候群の１例

A case of atypical neuroleptic malignant syndrome following discontinuation of many different neuroleptics and antidepressant agents is described. A 33-year-old woman with a 6-year history of depression and alcoholism had been treated with daily oral doses of 2mg of haloperidol, 75mg of clomipramine, 150mg of sulpiride, 150mg of trazodone, 3mg of etizolam, 3mg of biperidene, and 0.5g of disulfiram. She was admitted to a local hospital because of agitation and confusion. The patient refused all medication and her ingestion had markedly decreased. Six days after discontinuing her medication, she developed hypotension and was transferred to our institution. When brought to our emergency room, she was in shock with cold sweats, tachycardia, and consciousness disturbance. She became pyrexic, and 3 days after admission developed systemic tremor and oral dyskinesia. Her serum creatine phosphokinase levels gradually increased in spite of the improvement of her hemodynamic state. A diagnosis of atypical neuroleptic malignant syndrome was made, and treatment with dantrolene and bromocriptine was instituted. Her symptoms gradually subsided. This case suggests that development of neuroleptic malignant syndrome should be borne in mind whenever antipsychotic drugs are abruptly discontinued.

Use of clozapine in tardive dystonia

1. 1. This open clinical trial (N = 7) measured the course of severe tardive dystonia in chronic psychiatric patients after discontinuation of neuroleptics and subsequent use of clozapine. 2. 2. The dystonia was regularly assessed using the Fahn-Marsden Rating Scale. The eventual concomitant tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale. The mean follow up was 103 weeks. 3. 3. The results for the tardive dystonia: four patients recovered totally, two unproved considerably and one did not recover. 4. 4. The results for the concomitant tardive dyskinesia: five of the seven patients had also dyskinesia, one patient had a total, two a partly remission, one had a very fluctuating course, and one patient worsened. Another patient developed dyskinesia. 5. 5. It is suggested to consider clozapine for patients with tardive dystonia who have to continue antipsychotic treatment.

Neuroleptic malignant syndrome after neuroleptic discontinuation

1. 1. Neuroleptic withdrawal can cause autonomic and behavioral symptoms (nausea, vomiting, diarrhea, diaphoresis, myalgia, anxiety, restlessness) and movement disorders (withdrawal emergent parkinsonism, withdrawal dyskinesia, covert dyskinesia). 2. 2. Neuroleptic malignant syndrome (NMS) is a rare but extremely severe adverse reaction to neuroleptic drugs characterized by extrapyramidal and autonomic symptoms, altered level of consciousness and abnormal laboratory findings. 3. 3. Withdrawal neuroleptic malignant syndrome, though an even rarer condition (only 7 cases reported to date), should alert to consider the possibility that abrupt neuroleptic discontinuation can be complicated by NMS. 4. 4. The pathophysiology of withdrawal medical symptoms may be related to a cholinergic rebound; withdrawal neuroleptic malignant syndrome may be attributed to an “imbalance” in the dopaminergic system. 5. 5. The authors report two cases of NMS precipitated by the abrupt withdrawal of neuroleptic drugs.

Effects of brief neuroleptic discontinuation in chronic hospitalized schizophernic patients: no evidence for supersensitivity psychosis

As many as one third of patients suffering from schizophrenia have persistent severe psychotic symptoms despite high doses of neuroleptic treattaunt. Increased psychotic symptoms because of receptor sensitization psychosis has been proposed as possible side effects of chronic neuroleptic exposure. As part of a protocol to medicate chronic hospitalized treatment resistant schizophrenic patients (DSM-Ill-R and SADS/RDC) with clozapine, we evaluated the effects of discontinuing treatment with high doses of neuroleptics for evidence of a psychosis. Twenty chronic schizophrenic patients, hospitalized for at least 24 months, were tapered of all their neureleptic medication over an average of 42 days. All patients were on large doses of antipsychotic medication (mean + sd = 2058 4-1243 chlorpromazine equivalents). No significant differences were found in pairwise t-tests to evaluate BPRS scores between baseline, end of taper, one and three weeks medication free periods. Multivariate analysis for testing differences between BPRS subscales (positive, negative, agitation, affective) also showed no significant difference. in treatment-resistant chronic schizophrenic patients there is no evidence that high doses of neuroleptics are beneficial, as evidenced by the absence of any deterioration during a period of neuroleptic taper and withdrawal. There is also no support for the idea of a supersensitivity psychosis as evidenced by the absence of any increase in psychotic symptomatulogy.

Deficit symptoms in schizophrenia: negative symptoms versus neuroleptic-induced deficits.

Definitions of negative symptoms and deficit syndromes are reviewed in this article; rating scale criteria (the Scale for Assessment of Negative Symptoms and the Positive and Negative Syndrome Scale); Crow's type II syndrome; Carpenter's deficit syndrome; and the draft of DSM-IV. The core negative symptoms identified by these investigators also describe the neuroleptic-induced deficit syndrome (NIDS). Study designs and assessment methods to distinguish NIDS from the symptoms of schizophrenia are presented. Assessment methods include rating scales and a novel method that uses descriptive symptom vignettes. Designs include neuroleptic discontinuation studies, dose comparisons and comparison of atypical antipsychotic medicines to typical neuroleptic drugs.

Prolactin responses to im haloperidol in drug-naive and drug-experienced schizophrenic patients

SummaryThe prolactin (PRL) responses to 5 mg im haloperidol were assessed in the drug-free state and after one month treatment with neuroleptics in 14 male schizophrenic patients who had never received drug treatment, and in 20 male patients who had discontinued their neuroleptic treatment for periods of two months to one year. Drug experienced patients showed lower PRL increases after acute haloperidol (mean 31.7 ng/ml) than drug-naive patients (mean responses 43.4 ng/ml). After treatment with neuroleptics in doses appropriate for the best clinical response, the baseline PRL levels were similar in the two groups, and im haloperidol did not cause any further PRL increases. The results provide evidence that after discontinuation of neuroleptics, the hypothalamic-pituitary dopamine receptors are subsensitive, and remain in that state for long periods of time.