olanzapine and Substance-Withdrawal-Syndrome

Phenibut is a glutamic acid derivative with activity on the γ-aminobutyric acid (GABA)B, A, and B-phenethylamine receptors. It is prescribed in former Communist Bloc countries for anxiolysis and related psychiatric disorders. It can be easily obtained in Western countries and is thought to have abuse potential. Abrupt discontinuation has been reported to precipitate an abstinence syndrome. A review of the literature identified 22 reported cases, many of which were notable for severe psychomotor agitation and requirements for aggressive pharmacologic treatment. Neurologic and autonomic signs and symptoms may mimic serotonin or neuroleptic malignant syndrome. Patients were typically younger and had coexisting substance abuse disorders to other drugs. Also presented is a case of a 23-year-old male with an acute phenibut abstinence syndrome. This patient exhibited severe psychomotor agitation requiring physical restraints, dexmedetomidine, lorazepam, haloperidol, diphenhydramine, cyproheptadine, melatonin, olanzapine, and baclofen for symptom control.

Topics: Akathisia, Drug-Induced; Baclofen; Cyproheptadine; Dexmedetomidine; Diphenhydramine; GABA-A Receptor Antagonists; GABA-B Receptor Agonists; gamma-Aminobutyric Acid; Haloperidol; Humans; Lorazepam; Male; Melatonin; Neuroleptic Malignant Syndrome; Olanzapine; Receptors, GABA; Substance Withdrawal Syndrome; Substance-Related Disorders; Young Adult

A recent years' increase in both prescribing and availability of second-generation antipsychotics (SGAs) has been observed. According to the literature, typically made up by case studies/series, quetiapine seems to be the most commonly misused SGA, with both intranasal and intravenous intake modalities having been described. Another SGA that has been anecdotally reported to be misused is olanzapine. For these molecules, both a previous history of drug misuse and being an inmate have been described as factors associated with misuse. Hence, while providing here an updated literature review of the topic, we aimed at assessing all cases of quetiapine misuse/abuse/dependence/withdrawal as reported to the European Medicines Agency's EudraVigilance (EV) database; this was carried out in comparison with the reference drug olanzapine.. All spontaneous, European Medicines Agency database reports relating to both quetiapine (2005-2016) and olanzapine (2004-2016) misuse/abuse/dependence/withdrawal issues were retrieved, and a descriptive analysis was performed.. From the EV database, 18,112 (8.64% of 209,571) and 4178 (7.58% of 55,100) adverse drug reaction reports of misuse/abuse/dependence/withdrawal were associated with quetiapine and olanzapine, respectively. The resulting proportional reporting ratio values suggested that the misuse/abuse-, dependence-, and withdrawal-related adverse drug reactions were more frequently reported for quetiapine (1.07, 1.01, and 5.25, respectively) in comparison with olanzapine.. Despite data collection limitations, present EV data may suggest that, at least in comparison with olanzapine, quetiapine misuse may be a cause for concern.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Benzodiazepines; Child; Databases, Factual; European Union; Female; Humans; Male; Middle Aged; Olanzapine; Prescription Drug Misuse; Quetiapine Fumarate; Substance Withdrawal Syndrome; Substance-Related Disorders; Young Adult

Since cocaine and psychostimulant dependence are related to increased dopamine release, antipsychotics have been tried to reduce their reinforcing properties. A meta-analysis was undertaken to assess the efficacy and tolerability of antipsychotics in cocaine- or stimulant-dependent patients.. We searched PubMed, Cochrane Library databases, and PsycINFO from database inception until June 24, 2013, using the following keywords: (randomized OR random OR randomly) AND (placebo) AND (methylphenidate OR cocaine OR methamphetamine OR amphetamine OR 3,4-methylenedioxymethamphetamine) AND (dependence OR abuse) AND (antipsychotic OR neuroleptic OR 34 specific antipsychotic names).. Included were randomized, placebo-controlled trials of antipsychotics lasting at least 2 weeks in patients with primary cocaine or psychostimulant dependence. Of 363 hits, we removed 316 duplicates, 20 references based on abstract/title, and 13 ineligible full-text articles, retaining 14 trials for this meta-analysis.. Two authors independently extracted the data. Coprimary outcomes included degree of substance use and lack of abstinence. Risk ratio (RR), 95% CI, and standardized mean difference were calculated.. Ten studies in patients with primary cocaine dependence (risperidone = 5, olanzapine = 3, reserpine = 2; n = 562) and 4 in those with amphetamine/methamphetamine dependence (aripiprazole = 4; n = 179) were meta-analyzed (14 studies, total n = 741). When study results were pooled together, antipsychotics did not differ from placebo in regard to cocaine use days and lack of cocaine or amphetamine/methamphetamine abstinence, severity of addiction, cocaine or amphetamine/methamphetamine craving, Clinical Global Impressions-Severity of Illness (CGI-S) scores, depression, anxiety, compliance, all-cause discontinuation, and several side effects. However, antipsychotics caused more intolerability-related discontinuation than placebo (P = .0009). Individually, aripiprazole was superior to placebo in regard to CGI-S (P = .001), while olanzapine was inferior to placebo in regard to cocaine craving (P = .03) and risperidone was inferior to placebo in regard to depression (P = .002).. Antipsychotics had no advantages over placebo in regard to cocaine use and cocaine or psychostimulant abstinence or craving, while causing more intolerability-related discontinuations.

Topics: Amphetamine-Related Disorders; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Central Nervous System Stimulants; Cocaine; Cocaine-Related Disorders; Dopamine; Dopamine Uptake Inhibitors; Humans; Methamphetamine; Olanzapine; Outcome Assessment, Health Care; Piperazines; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Substance Withdrawal Syndrome; Synaptic Transmission; Treatment Outcome

Given the problematic nature of tardive dyskinesia in persons taking conventional antipsychotics, evaluation of newer atypical antipsychotic agents should include a systematic assessment of tardive dyskinesia liability. Results of a prospective double-blind, randomized study of schizophrenic patients who participated in 3 preclinical olanzapine studies and were treated with 5 to 20 mg/day of olanzapine (N = 1192) or haloperidol (N = 522) recently indicated a significantly lower risk of development of tardive dyskinesia with olanzapine treatment than haloperidol treatment. This article discusses the known effects of atypical antipsychotic medications on tardive dyskinesia movements (both withdrawal and persistent) and the incidence rate of tardive dyskinesia among schizophrenic patients undergoing long-term treatment with olanzapine or haloperidol.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Haloperidol; Humans; Incidence; Molindone; Olanzapine; Pirenzepine; Prospective Studies; Risk Factors; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Survival Analysis

The enthusiasm produced by the introduction of antipsychotic medication in the 1950s gave way to a certain frustration in the 1970s and 1980s. Despite the development of a large number of new drugs, little progress was made in treatment because these new agents were, in essence, therapeutically equivalent. This lack of progress was perhaps also related to an emphasis on tardive dyskinesia in the 1970s, i.e., the preoccupation with a negative effect of treatment. The reverse is taking place today. Clozapine and the other atypical antipsychotics are associated in people's minds with fewer or absent extrapyramidal symptoms and less tardive dyskinesia than the older typical agents. As a result, a certain amount of complacency exists. Tardive dyskinesia not only may be painful and disfiguring, but it also predicts poor outcome in patients with schizophrenia. Although many treatments have been tried, none have proven completely efficacious. The best treatment for tardive dyskinesia and dystonia is prevention, which is a function of medication choice. Pharmacologic interventions for tardive dyskinesia include clozapine and the other atypical antipsychotics. If typical antipsychotics must be used, they should be started at the lowest possible levels. Studies of risperidone suggest that it, too, should be used at very low doses to minimize the risk of tardive dyskinesia. It is also possible that schizophrenic patients taking atypical antipsychotics may experience fewer spontaneous dyskinesias, although further study is warranted.

Topics: Adult; Akathisia, Drug-Induced; Algorithms; Antipsychotic Agents; Benzodiazepines; Clozapine; Decision Trees; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Male; Olanzapine; Pirenzepine; Probability; Reserpine; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Tetrabenazine; Treatment Outcome; Vitamin E

The incidence of acute extrapyramidal symptoms (EPS)--akathisia, dystonia, and parkinsonism--associated with traditional antipsychotics varies, but most researchers agree that neuroleptic-induced EPS occur in 50% to 75% of patients who take conventional antipsychotics. Atypical antipsychotics were developed to widen the therapeutic index and to reduce EPS. Although the mechanisms are unclear, the risk of EPS is less with the novel antipsychotics than with conventional drugs, and agents that produce low levels of acute EPS are likely to produce less tardive dyskinesia. Nevertheless, clinicians should exercise caution when comparing data from investigations of the novel antipsychotics and, until long-term data become available, should administer the new drugs at doses below the EPS-producing level.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance Withdrawal Syndrome

Topics: Administration, Oral; Adult; Aged; Clonidine; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Opioid-Related Disorders; Prospective Studies; Severity of Illness Index; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Hyperprolactinemia, an adverse effect associated with the use of typical antipsychotics and the atypical antipsychotic risperidone, has both acute and chronic clinical consequences. One option for clinical management is switching to an agent with a lower liability for inducing hyperprolactinemia. This post-hoc sub-analysis of an 8-week, open-label study in outpatients with schizophrenia (CN138-215) examined short-term effects on prolactin levels during a switch from risperidone or olanzapine to aripiprazole 30 mg/day. Three switch strategies were used: (I) immediate aripiprazole initiation with simultaneous immediate discontinuation of olanzapine/risperidone; (II) immediate aripiprazole initiation while tapering off olanzapine/risperidone over 14 days; (III) titrating aripiprazole upwards while tapering off olanzapine/risperidone over 14 days. Changes in prolactin levels from baseline to each last observation carried forward time point were compared with t-tests using Bonferroni correction for multiple comparisons. This sub-analysis included 269 subjects: 105 previously treated with risperidone; 164 previously treated with olanzapine. Mean baseline prolactin levels (ng/mL) were within normal range for the three olanzapine groups (Group-I, 11.7; Group-II, 13.2; Group-III, 11.2), but above normal for the risperidone groups (Group-I, 39.7; Group-II, 48.5; Group-III, 33.5). Following aripiprazole initiation, mean prolactin levels decreased significantly (p<0.001) at week-1 and were maintained to week-8 in all groups irrespective of prior treatment. Previously elevated prolactin levels in the risperidone groups were reduced to within normal range within 1 week, irrespective of switching strategy. Tolerability was good regardless of prior medication or switching strategy. Overall, rapid decreases of prolactin levels were achieved safely with all three aripiprazole switching strategies. Reversal of hyperprolactinemia during the crossover period indicates the safety and potential utility of aripiprazole addition in patients with elevated prolactin.

Topics: Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Piperazines; Prolactin; Psychotic Disorders; Quinolones; Risperidone; Schizophrenia; Sex Factors; Substance Withdrawal Syndrome; Young Adult

Olanzapine (OLAN), an atypical antipsychotic medication with mixed 5-HT2/DA antagonist properties, was predicted to dose-dependently decrease urge to smoke, withdrawal, and cigarette reinforcement in smokers without psychosis. A double-blind placebo-controlled within-subjects cross-over trial investigated the acute effects of OLAN (0, 2.5, and 5.0 mg; counterbalanced order) in 24 community smokers who underwent 10-hr smoking deprivation. Urge to smoke, tobacco withdrawal, and cigarette reinforcement were assessed with cue reactivity and behavioral choice procedures. OLAN (2.5 mg) reduced withdrawal symptoms before and during cue exposure and decreased urge associated with anticipated positive affect from smoking before and during cue exposure; 5.0 mg OLAN decreased withdrawal only when cues were included. OLAN did not affect preference for cigarette puffs versus money, smoke intake, or urge to smoke associated with negative affect relief. The results indicate a potentially beneficial effect of 2.5 mg OLAN on tobacco withdrawal and urge to smoke. Combined 5HT/DA antagonists should be considered for future development of pharmacotherapies for smoking cessation.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cross-Over Studies; Cues; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Individuality; Male; Middle Aged; Nicotine; Nicotinic Agonists; Olanzapine; Patient Compliance; Smoking; Smoking Cessation; Substance Withdrawal Syndrome

To more clearly clarify the efficacy of the atypical antipsychotics compared to conventional antipsychotics, we add data on the outcome of patients diagnosed with schizophrenia from two large, international clinical trials comparing olanzapine with haloperidol (n = 1996) and olanzapine with risperidone (n = 339). Both studies comprised double-blinded, placebo controlled, random assignment trials. Health outcomes reported include: (i) time to discontinuation in the trial; (ii) clinical relapse; and (iii) time to drug non-compliance. When outcome was measured as time to discontinuation due to adverse events or lack of efficacy, olanzapine showed superiority over haloperidol and no difference compared to risperidone. Of those patients who had an initial response, there was no significant difference between olanzapine and haloperidol when outcome was measured using either: (i) 52-week relapse rates or (ii) time to first non-compliance. Using the measures of study discontinuation, relapse and non-compliance, in one trial the atypical antipsychotic olanzapine was superior to haloperidol, while in a second trial there were no differences between olanzapine and risperidone.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Recurrence; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Survival Analysis; Time Factors; Treatment Outcome; Treatment Refusal

Given the problematic nature of tardive dyskinesia in persons taking conventional antipsychotics, evaluation of newer atypical antipsychotic agents should include a systematic assessment of tardive dyskinesia liability. Results of a prospective double-blind, randomized study of schizophrenic patients who participated in 3 preclinical olanzapine studies and were treated with 5 to 20 mg/day of olanzapine (N = 1192) or haloperidol (N = 522) recently indicated a significantly lower risk of development of tardive dyskinesia with olanzapine treatment than haloperidol treatment. This article discusses the known effects of atypical antipsychotic medications on tardive dyskinesia movements (both withdrawal and persistent) and the incidence rate of tardive dyskinesia among schizophrenic patients undergoing long-term treatment with olanzapine or haloperidol.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Haloperidol; Humans; Incidence; Molindone; Olanzapine; Pirenzepine; Prospective Studies; Risk Factors; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Survival Analysis

The abrupt appearance of clozapine discontinuation symptoms represents a particularly unique situation that has not been characterized in a double-blind, placebo-controlled trial. A randomized, double-blind comparison of placebo (N = 53) and olanzapine 10 mg (N = 53) for 3 to 5 days following the abrupt discontinuation of clozapine (< 300 mg/day) was carried out. Subjects were assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale of Severity, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Mini-Mental State Evaluation. Subsequently both groups received open-label olanzapine (10-25 mg/day) for an additional 9 weeks. Statistically significantly more placebo-treated (24.5%) than olanzapine-treated (7.5%) patients experienced clozapine discontinuation symptoms (p = 0.017). Core symptoms included delusions, hallucinations, hostility, and paranoid reaction and translated into a significantly higher worsening from baseline on the PANSS total, PANSS General Psychopathology subscale, and MADRS among subjects randomly assigned to receive placebo. After open-label treatment with olanzapine for 9 weeks, both groups were clinically stable, suggesting that the discontinuation symptoms were transient. However, subjects who had been randomly assigned to the 3- to 5-day placebo discontinuation segment achieved somewhat less global clinical improvement. Although a pharmacologic interpretation is speculative, evidence of a clozapine discontinuation syndrome was apparent. In most cases, the direct substitution of a pharmacologically similar agent (olanzapine) prevented the syndrome. Clozapine discontinuation or noncompliance should be considered in the differential assessment of an acutely emergent psychosis. The possibility that subjects who experience a clozapine discontinuation syndrome may take longer or are less likely to clinically restabilize warrants further investigation.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia; Substance Withdrawal Syndrome

Topics: Administration, Cutaneous; Analgesics, Opioid; Fentanyl; Humans; Naltrexone; Olanzapine; Substance Withdrawal Syndrome

Topics: Adult; Akathisia, Drug-Induced; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Humans; Ketamine; Male; Olanzapine; Substance Withdrawal Syndrome

We report the case of two young subjects who developed an obsessive-compulsive disorder (OCD) during a heavy use of ecstasy. After several months of discontinuation of the drug, major depression with psychotic features developed in one subject and a psychotic disorder in the other individual. No mental disorder preceded the use of ecstasy in any subject.. A familial and personality vulnerability for mental disorder was revealed in one subject, but not in the other, and all physical, laboratory and cerebral NMR evaluations showed normal results in both patients. Remission of OCD and depressive episode or psychotic disorder was achieved after treatment with a serotoninergic medication associated with an antipsychotic.. The heavy long-term use of ecstasy may induce an alteration in the brain balance between serotonin and dopamine, which might constitute a pathophysiological mechanism underlying the onset of obsessive-compulsive, depressive and psychotic symptoms. The heavy use of ecstasy probably interacted with a vulnerability to psychiatric disorder in one subject, whereas we cannot exclude that an "ecstasy disorder" ex novo affected the other individual.

Topics: Adolescent; Amphetamine-Related Disorders; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Borderline Personality Disorder; Brain; Clomipramine; Comorbidity; Depressive Disorder, Major; Dopamine; Female; Genetic Predisposition to Disease; Hallucinogens; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine; Obsessive-Compulsive Disorder; Olanzapine; Psychoses, Substance-Induced; Risk Factors; Risperidone; Serotonin; Substance Withdrawal Syndrome; Young Adult

The present study was designed to investigate the effects of olanzapine, a serotonin-dopamine antagonistic atypical antipsychotic agent, on ethanol withdrawal syndrome in rats. Adult male Wistar rats were subjects. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair fed with an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. After 2nd, 4th and 6th h of ethanol withdrawal, rats were observed for 5 min, afterwards withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behavior, tremor, wet dog shakes, abnormal posture and abnormal gait were recorded or rated. Olanzapine (0.5, 1 and 2 mg/kg) and saline were injected to the rats intraperitoneally 30 min before ethanol withdrawal assessment. A second series of injections was also given 30 min before the 6th-h-observation, and subjects were then tested for audiogenic seizures. Olanzapine (2 mg/kg) produced significant inhibitory effects on stereotyped behaviors and wet dog shakes at the 6th h of ethanol withdrawal. Contrary, the same dose caused some increases in the intensity of posture and gait impairments at the 2nd h of ethanol withdrawal. In addition, that dose was found to be ineffective on agitation, tremor, tail stiffness and audiogenic seizures. Our results suggest that acute olanzapine treatment has beneficial effects on stereotyped behavior and wet dog shakes, but it also has some adverse effects on posture and gait during ethanol withdrawal in rats. Overall, olanzapine does not seem to be an adequate and suitable drug in controlling of ethanol withdrawal syndrome.

Topics: Animals; Benzodiazepines; Central Nervous System Depressants; Dose-Response Relationship, Drug; Ethanol; Male; Motor Activity; Olanzapine; Rats; Rats, Wistar; Selective Serotonin Reuptake Inhibitors; Stereotyped Behavior; Substance Withdrawal Syndrome

Following the presentation of a case study and an overview of current data highlighting the need for further research into the use of antipsychotic medication during pregnancy, the aim of the present paper was to outline the establishment of, and present preliminary data from, the National Register of Antipsychotic Medication in Pregnancy (NRAMP).. Australian women with a history of psychosis, including schizophrenia, bipolar affective disorder with psychosis, schizoaffective disorder and first-episode psychosis, who are pregnant, are currently being invited to participate. The confluence of speculated national pregnancy rates and epidemiological data regarding child-bearing-age women with psychosis suggested an enrollment target of 100 women over a 24 month period. Details of antipsychotic medication are recorded throughout the pregnancy and for 1 year postnatally. Interviews with the mother are conducted 6 weekly antenatally, and then at 6 and 12 weeks, and 6 and 12 months postnatally, to assess symptoms of psychosis and depression, and attitudes towards parenting. In addition, consultations are conducted with the women's health-care providers to collate information regarding pharmacology and related side-effects, obstetric outcomes, psychiatric diagnoses and symptoms during pregnancy and for 1 year after delivery, and the provision of details on the baby's health and well-being.. NRAMP was launched in 2005. Ethics approvals have been gained at 14 sites nationally. Thirty women have consented, and 11 have completed. Data including demographics, health-care provision and medication for the first 30 participants are presented.. The establishment of NRAMP is an important strategy in improving the management of serious mental illness such as schizophrenia and related disorders, in women who are pregnant. This project involves extensive collaboration between many different clinical groups and industry, and shall culminate in an important resource to improve the quality of life for both patients and future generations.

Topics: Adult; Antipsychotic Agents; Australia; Benzodiazepines; Chlorpromazine; Cross-Sectional Studies; Data Collection; Female; Humans; Infant, Newborn; Olanzapine; Phenytoin; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Psychotic Disorders; Registries; Risk Factors; Substance Withdrawal Syndrome; Suicide

This article provides an introduction to the complex issues surrounding the management of women who have a history of psychosis and who become pregnant. Balancing the mental wellbeing of the woman and the safety and wellbeing of the baby is a complex task for both the expectant mother and the health professionals involved in her care.. Within this article the complexity of the issues will be outlined as a case report of a woman with a history of psychotic related disorders, who was also pregnant.. The woman was being case managed by a Mental Health Service in Victoria, Australia, and was included on the National Register of Antipsychotic Medications in Pregnancy Register (NRAMP) recently established at the Alfred Psychiatry Research Centre (APRC).. The profile of women with a history of previous mental illness, and who are pregnant, often includes a poor psychosocial history and involvement with child protection agencies with regard to custody of the children. Well meant but poorly coordinated decisions by health professionals result in sub-optimal outcomes for both mother and infant.. There is a need for the exploration of the management and experiences of women who have a history of psychosis and who are pregnant. This case example highlights the complexity of issues surrounding the management of this vulnerable group of women and their babies.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Case Management; Child Custody; Cooperative Behavior; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn; Infant, Small for Gestational Age; Interprofessional Relations; Olanzapine; Pregnancy; Pregnancy Complications; Psychotic Disorders; Puerperal Disorders; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Treatment Outcome

There is controversy over whether exposure to stress precipitates relapse and/or increases alcohol (ethanol) intake. Our laboratory has demonstrated that repeated stress prior to withdrawal from a brief forced exposure to alcohol results in withdrawal-induced anxiety-like behavior. Because anxiety is often regarded as a precipitating factor in relapsing alcoholics, we decided to examine the consequences of stressing alcohol-preferring P rats on both voluntary alcohol drinking and withdrawal-induced anxiety.. P rats were subjected to 3 cycles of 5 days of voluntary alcohol drinking and 2 days of deprivation. Restraint stress (60 min) was applied to some animals during the first and second deprivations/withdrawals (at 4 h). Drugs (flumazenil, buspirone, SB242,084, CP154,526, CRA1000, naloxone, haloperidol, olanzapine, naloxone, and haloperidol) were given to some rats 30 min prior to restraint stress.. Stressed, deprived P rats exhibited both a longer duration of elevated alcohol drinking and anxiety-like behavior in the social interaction test upon withdrawal after the third cycle of voluntary alcohol drinking. When given prior to each of the restraint stresses, the benzodiazepine receptor antagonist flumazenil (5 mg/kg), the corticotrophin releasing factor receptor antagonists CRA1000 (3 mg/kg) and CP154,526 (10 mg/kg), the serotonin 5-HT(1A) receptor partial agonist buspirone (0.6 mg/kg), and the mixed 5-HT(2C)/D2 receptor antagonist olanzapine were effective in reducing the increased duration of elevated alcohol drinking and the withdrawal-induced anxiety-like behavior. In contrast, while the opiate receptor antagonist naloxone (20 mg/kg), the 5-HT(2C) receptor antagonist SB242084 (3 mg/kg), and the dopamine receptor antagonist haloperidol (0.1 mg/kg) also reduced drinking, they did not significantly alter anxiety like behavior.. These results suggest that stress-induced facilitation of alcohol drinking and withdrawal-induced anxiety-like behavior in P rats may be closely but imperfectly linked.

Topics: Alcohol Drinking; Aminopyridines; Animals; Anti-Anxiety Agents; Anxiety; Behavior, Animal; Benzodiazepines; Buspirone; Dopamine Antagonists; Ethanol; Flumazenil; GABA Modulators; Haloperidol; Indoles; Naloxone; Narcotic Antagonists; Olanzapine; Rats; Rats, Inbred Strains; Restraint, Physical; Serotonin Receptor Agonists; Stress, Physiological; Substance Withdrawal Syndrome

In female rats olanzapine (4 mg/kg b.i.d., i.p.) induced acute hypothermia, followed by very rapid full tolerance. With more prolonged treatment (over > 10 days) the hypothermic effect of olanzapine was reinstated. Subsequent withdrawal after 18 days of treatment induced very rapid onset (within 1 day) hyperthermia, which was time limited, dissipating completely over 3-4 days. These findings are similar to previous findings with clozapine [Goudie A Smith J Robertson A Cavanagh C (1999). Clozapine as a drug of dependence. Psychopharmacology; 142: 369-374.]. Although the mechanism(s) involved in the secondary hypothermic effect of olanzapine are, at present, unclear; the withdrawal hyperthermia observed represents the first report of a clear discontinuation effect of olanzapine. Such discontinuation effects are probably observed with many antipsychotic drugs. Since they have been suggested to facilitate relapse to psychosis and to interfere with subsequent clinical responses to antipsychotics, they merit further detailed analysis in both clinical and preclinical studies.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Body Temperature; Drug Tolerance; Female; Fever; Olanzapine; Rats; Rats, Wistar; Substance Withdrawal Syndrome

GHB is an increasingly popular drug of abuse that can be associated in select cases with growing dependence and a severe withdrawal syndrome. While benzodiazepines are recommended for treatment of the withdrawal syndrome, some cases have been described as benzodiazepine-resistant. The authors describe treatment of such a case, which was unsuccessfully treated initially with benzodiazepines, then successfully treated with adjuvant atypical neuroleptics, and offer a possible neurochemical explanation for why such agents may be theoretically more effective than benzodiazepines in treating GHB withdrawal.

Topics: Adjuvants, Anesthesia; Adult; Antipsychotic Agents; Benzodiazepines; Humans; Hydroxybutyrates; Male; Olanzapine; Substance Withdrawal Syndrome; Treatment Failure

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Therapy, Combination; Electroencephalography; Epilepsy, Complex Partial; GABA Agonists; Humans; Male; Nipecotic Acids; Olanzapine; Substance Withdrawal Syndrome; Tiagabine

Topics: Antipsychotic Agents; Benzodiazepines; Citalopram; Drug Therapy, Combination; Humans; Olanzapine; Paroxetine; Pirenzepine; Risk Factors; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Substance Withdrawal Syndrome

Topics: Antipsychotic Agents; Appetite; Appetite Depressants; Benzodiazepines; Central Nervous System Stimulants; Delusions; Depressive Disorder; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ephedrine; Euphoria; Female; Hallucinations; Haloperidol; Humans; Long-Term Care; Mazindol; Middle Aged; Olanzapine; Psychoses, Substance-Induced; Recurrence; Substance Withdrawal Syndrome; Substance-Related Disorders; Thioridazine

Antipsychotic drugs have been reported to increase the expression of subunits of the NMDA receptor at the level of mRNA but it is not clear whether such effects are apparent at the level of the radioligand binding or receptor protein. Therefore, we examined the effect of treatment of, and withdrawal from, haloperidol, chlorpromazine, olanzapine or clozapine on the binding of [3H]N-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP ) to the open ion channel of the NMDA receptor in rat caudate-putamen, hippocampus and frontal cortex. [3H]TCP binding was not significantly different in the caudate-putamen, hippocampus and cortex after three months of treatment with any antipsychotic drug. There were significant decreases in [3H]TCP binding in rat caudate-putamen and cortex, but not hippocampus, one month after ceasing treatment. Decreases in the caudate-putamen were detected in rats previously treated with chlorpromazine (0.1 mg/kg/day) and clozapine (0.1 and 1.0 mg/kg/day). In the cortex, decreases in [3H]TCP binding were also detected in rats previously treated with olanzapine (0.1 mg/kg/day) for three months. These data suggest that changes in the NMDA receptor associated ion channels occur following antipsychotic drug withdrawal.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Brain; Chlorpromazine; Clozapine; Haloperidol; Ion Channels; Male; Olanzapine; Phencyclidine; Pirenzepine; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Substance Withdrawal Syndrome

Novel antipsychotic drugs (APDs) have enhanced therapeutic actions compared to 'typical' APDs. However, clinical studies indicate that some induce marked weight gain. We attempted to model this effect in female Wistar rats given olanzapine chronically at 4 mg/kg b.i.d (4.5 h between injections). Such rats showed marked weight gain, which was statistically significant after only a single day of treatment, although weight gain increased up to a plateau after 10 days of treatment. Cessation of treatment led to rapid weight loss, which was significant after a single day of withdrawal. The weight gain observed was characterized by marked individual differences. As some clinical reports suggest that novel APD-induced weight gain is most pronounced in patients with the lowest body weight, we examined the relationship between weight gain and baseline body weight. However, we observed no significant relationship between baseline body weight and weight gain. The observation that olanzapine can induce weight gain rapidly in rats, in conjunction with the observation of marked individual differences in weight gain, suggests that patients at risk of developing weight gain might be detectable early in treatment. Furthermore, the finding that weight gain is rapidly reversible suggests that patients at risk of weight gain could be switched to APDs with less pronounced tendencies to induce weight gain. The study of APD-induced weight gain in rodents may provide insights into the nature, causes, and treatments for, novel APD-induced weight gain in the clinic. However, it remains to be determined how closely rodent models mimic the clinical situation and whether the mechanism(s) involved in the weight gain we have observed are the same as those involved in the clinical use of these drugs.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Female; Olanzapine; Pirenzepine; Rats; Rats, Wistar; Substance Withdrawal Syndrome; Weight Gain

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychoses, Substance-Induced; Recurrence; Schizophrenia; Substance Withdrawal Syndrome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Myoclonus; Olanzapine; Pirenzepine; Schizophrenia, Paranoid; Substance Withdrawal Syndrome

Withdrawal symptoms associated with switch between two typical antipsychotics are generally rare and mild. In contrast, switching from clozapine to risperidone can be lead to severe withdrawal symptoms. Different pathophysiologic aetiologies have been suggested for explaining these severe symptoms, including cholinergic supersensitivity and rebound. Theoretically, the switch from clozapine to olanzapine should not lead to any problems because those two agents have the same affinity in vitro for muscarinic receptors.. This study reports two cases of switches from clozapine to olanzapine, in refractory schizophrenic patients, which were associated with severe withdrawal symptoms.. After the switch, the two patients developed diaphoresis, hypersialorrhea, bronchial obstruction, agitation, anxiety and enuresis. The symptoms were treated with anticholinergic medication and by an increase in dose of olanzapine to 20 mg/day. For one of the patients this treatment led to normalization of secretion. For the other patient, a superinfection leading to a bilateral pneumopathy which required emergency hospitalization in a general hospital was observed.. The symptomatology and the response to treatment lead to the hypothesis of a muscarinic from abrupt weaning. The withdrawal symptoms disappeared rapidly with an increase in olanzapine dosage and with anticholinergic started at the beginning of the switch. We recommend slow clozapine weaning over 3 weeks or more with concurrent anticholinergic treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Receptors, Muscarinic; Schizophrenia; Substance Withdrawal Syndrome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Combined Modality Therapy; Depressive Disorder; Electroconvulsive Therapy; Humans; Koro; Male; Olanzapine; Pirenzepine; Substance Withdrawal Syndrome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Administration Schedule; Hospitalization; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia; Substance Withdrawal Syndrome

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Biperiden; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Olanzapine; Pirenzepine; Schizophrenia; Substance Withdrawal Syndrome

The purpose of this study was to compare the subchronic, low-dose effects of clozapine with those of olanzapine in a learned behavioral task previously shown to distinguish between clozapine and haloperidol with acute and subchronic treatment regimes. Rats were trained to use a single forelimb to press a force-recording operandum and simultaneously to lick water from a dipper that remained available while forelimb force exceeded a modest lower limit. Analysis of the resulting forcetime recordings provided measures of task engagement (time on task-analogous to response rate), lick rhythm, tremor, ballistic (maximum force) and tonic (hold force) forelimb force measures, as well as the durations of the individual responses. In a between-groups dosing design, five separate groups of rats received vehicle, clozapine 1.0 or 5.0 mg/kg, olanzapine 0.5 or 1.0 mg/kg daily for 27 days. A 7-day withdrawal period followed. On days 22 and 26 of antipsychotic drug treatment, all rats additionally received 0.3 mg/kg trihexyphenidyl or 1.0 mg/kg quipazine, respectively. The effects of olanzapine and clozapine were similar in that both drugs reduced time on task, increased response duration, and slowed lick rhythm. The two drugs differed in that clozapine reduced the force and tremor measures but olanzapine did not. Both tolerance and withdrawal effects, as reflected by the tremor measure, were observed for clozapine but not for olanzapine. Trihexyphenidyl further increased the duration of responses already lengthened by clozapine; in contrast, trihexyphenidyl decreased the duration lengthening effect of olanzapine. Taken together, the results indicated that olanzapine did not have the antitremor and hypotonic effects displayed by clozapine, and olanzapine did not induce tolerance and withdrawal phenomena as clozapine did.

Topics: Animals; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Tolerance; Forelimb; Male; Muscarinic Antagonists; Olanzapine; Pirenzepine; Quipazine; Rats; Rats, Sprague-Dawley; Serotonin Receptor Agonists; Substance Withdrawal Syndrome; Tremor; Trihexyphenidyl