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Opioid antagonists block opioid receptors, a mechanism associated with utility in several therapeutic indications. Here, we review the sites of action, clinical uses, pharmacology, and general safety profiles of US Food and Drug Administration (FDA)-approved opioid antagonists. A review of the literature and product labels of opioid antagonists was conducted. The unique clinical uses of approved opioid antagonists are related to their ability to block opioid receptors centrally and/or peripherally. Centrally acting opioid antagonists treat opioid and alcohol use disorders (AUDs) and reverse opioid overdose. Because the opioid system influences weight and metabolism, one opioid antagonist combination product is approved for chronic weight management; another, approved for adults with schizophrenia or bipolar I disorder, mitigates olanzapine-associated weight gain. Peripherally acting opioid antagonists are approved for opioid-induced constipation; another accelerates gastrointestinal recovery after bowel surgery. Opioid antagonists are generally well tolerated; they are not associated with physiologic dependence or abuse. However, opioid antagonists can precipitate acute opioid withdrawal in patients using or undergoing withdrawal from opioid agonists. Likewise, their use can confer a risk for opioid overdose if attempts are made to overcome opioid antagonist blockade of opioid receptors via the intake of additional opioids. Opioid receptor antagonists have diverse therapeutic benefits based on their respective pharmacology and sites of action; understanding their respective nuances facilitates the safe and effective use of these agents.
Working as a consultant psychiatrist and started doing GMC. I Depressed again and tried various antidepressants, hating being off work. Admitted to the Scottish Borders Hospital, where I had been a consultant, and had ECT; I also started olanzapine and put on a lot of weight. A change in psychiatrist and also in diagnosis was difficult.
Amenorrhea secondary to hyperprolactinemia is one of the frequent adverse effects associated with the use of atypical antipyschotics. It is often neglected but can interrupt the compliance of treatment. Several studies indicate that olanzapine does not significantly affect serum prolactin levels in the long term, although contrary has been observed in few case reports.
Objectives
To report a case of olanzapine-induced amenorrhea due to hyperprolactinemia.
Methods
A 27-year-old woman with history of stillbirth 5 months prior, presented to OPD with hallucinatory behaviour and socio-occupational dysfunction for 5 months. She was on tianeptine 12.5 mg, escitalopram 10 mg and alprazolam 0.5 mg at presentation and was having regular menses. On assessment, she was diagnosed with unspecified psychosis. Her ongoing medications were stopped and she was started on Olanzapine (optimized to 20 mg/day) after which she reported significant improvement however developed amenorrhea within next 2 months hence advised to consult Obgyn. Urine pregnancy test came out negative and prolactin level was found to be 64.2 ng/ml. Other investigations including MRI were within normal limit. Olanzapine was cross tapered with Aripiprazole (maintained at 10 mg/day). Clonazepam was advised SOS for anxiety.
Results
After 1 month of aripiprazole treatment, monthly menses resumed and prolactin level returned to normal range. No biological dysfunction or other side effects were reported by the patient.
Conclusions
Olanzapine-induced amennorhea secondary to hyperprolactinemia, is a rare but possible event. We report a case in which olanzapine induced amenorrhea normalized after switching to aripiprazole. Baseline prolactin level should be obtained as they help in the management of patients with neuroleptic-induced hyperprolactinemia.
Hyperprolactinemia is a common unwanted antipsychotic-induced adverse effect, particularly in female patients, and can induce poor adherence to treatment. Aripiprazole is an antipsychotic with partial agonist activity over the dopamine D2 receptors which can be effective in reducing hyperprolactinemia in patients treated with antipsychotics.
Objectives
We investigate the efficacy of adjunctive treatment with aripiprazole for olanzapine-induced hyperprolactinemia and related hormonal side effects (amenorrhea, oligomenorrhea) in female patients with schizophrenia.
Methods
Eight female patients (22 to 40 years old) participated in this study with a diagnosis of schizophrenia and hyperprolactinemia-related hormonal side effects (amenorrhea, oligomenorrhea). Patients were treated with aripiprazole 10 mg/day added to a fixed olanzapine dose of 20 mg/day. Serum prolactin levels were measured at baseline and after 2, 4, 6, and 8 weeks. Symptoms and side effects were assessed using the Brief Psychiatric Rating Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale.
Results
Adjunctive treatment with aripiprazole resulted in significantly lower prolactin levels beginning at week 2. 87.5 % of patients at week 8 had prolactin levels normalize. Among 8 patients with menstrual disturbances, 75% of patients regained menstruation during the study. No significant changes were observed regarding psychopathology and adverse effect ratings.
Conclusions
Adjunctive aripiprazole treatment is effective for resolving olanzapine-induced hyperprolactinemia and reinstatement of menstruation in female patients, provides significant improvement and it appears to be safe with a lower risk of metabolic syndrome, without increased risk of adverse effects.
Over time the prevalence of methamphetamine associated psychosis (MAP) has increased globally including Asia and Europe. Shoptaw et al looked at an RCT and concluded that olanzapine is superior to haloperidol in terms of tolerability and the side effect profile as it causes fewer extrapyramidal symptoms. Another study by Xue et al compared the efficacy of olanzapine and haloperidol and found that they had comparable effects but the onset time in the olanzapine group was significantly earlier than the haloperidol group. Srisurapanont et al analyzed 6 RCTs and concluded that quetiapine and olanzapine are probably superior than aripiprazole and risperidone.
Objectives
The purpose of this review is to find out if olanzapine is better than other antipsychotics in treating methamphetamine-induced psychosis.
Methods
PubMed, SCOPUS, and Web of Science literature databases were screened and filtered by using specific search terms, inclusion/exclusion criteria. Texts of the selected articles and trials were reviewed and the search terms generated a total of 248 results from the databases. After applying the criteria 200 citations were left and 15 papers were reviewed.
Results
The literature review concluded that olanzapine can be used as an effective treatment for methamphetamine-induced psychosis. Olanzapine can help to reduce the psychotic symptoms in MAP with a quicker onset and lesser side effects.
Conclusions
Olanzapine can help in the treatment of methamphetamine-associated psychosis and can be considered as the first-line therapy. Research is further needed with a higher pool of candidates in the future to compare the efficacy and tolerability of different typical and atypical antipsychotics.
Atypical neuroleptics such as olanzapine are indicated for the treatment of various psychiatric disorders and have been used in the palliative care setting also for several clinical indications. Peripheral and facial edema are a rare side effect of the treatment with olanzapine. We report a case of an advanced cancer patient cared receiving palliative care who developed severe facial edema after initiating a low dose of olanzapine in monotherapy.
Method
A patient with advanced cancer who presented with severe facial edema after initiating olanzapine for the treatment of her opioid use disorder.
Results
After excluding other differential diagnosis for facial edema, olanzapine was discontinued with complete resolution of the edema.
Significance of results
To the best of our knowledge, this is the first case reporting facial edema due to olanzapine treatment in a patient with advanced cancer. Our report will help clinicians recognize the possible role of olanzapine in cases of rapid onset of facial edema, allowing its rapid resolution.
Bipolar disorder is a serious psychiatric condition based on depressive, manic, and mixed phases. Bipolar disorder has been usually divided into type I (manic phases and depressive phases) and type II (hypomanic and depressive phases). Furthermore, subsequent classifications have been developed based on subtypes complexity.
Objectives
A case of a 52-year-old man is presented. The patient had suffered depressive symptoms and self-destructive ideation. He had sold his house to pay for drugs and prostitution, even though he was in quarantine for COVID-19. The patient had a history of depressive episodes with milder manic episodes which had been treated with antidepressants.
Methods
Analytical and imaging tests were performed without findings. Mood stabilizing treatment was started based on lithium salts. He became perplexed and suspicious of the medication. Auditory hallucinations appeared congruent with the mood and he began to think that his relatives were dead; the patient started to communicate via telephone with actors. A treatment based on olanzapine 30mg/d was started.
Results
The clinic was resolved with antipsychotic treatment. The diagnosis of Bipolar Disorder has been made in youth; however, some patients symptoms could be camouflaged and allow a functional life. Depressive episodes could present with psychotic symptoms and predispose more to suicide attempts than manic phases.
Conclusions
The early-stage diagnosis should play a key role on bipolar disorder control. More public and clinic efforts are needed to prevent non-easily distinguishable cases which could derived on serious social and health problems.
Clozapine is generally considered as the treatment of choice for patients with treatment-resistant schizophrenia (TRS). However, its superiority has recently been questioned because olanzapine has been suggested as non-inferior to clozapine in its effectiveness.
Aims
We aimed to investigate the current status of clozapine prescriptions to identify any disparity between clinical guidelines and real-world practices.
Method
In this study, we utilised the Health Insurance Review Agency database in the Republic of Korea to investigate the real-world effectiveness of clozapine for patients with TRS. We compared differences in patient variables before and after clozapine administration, and we also performed survival analyses for both psychiatric admissions and emergency room visits among patients who used clozapine or olanzapine.
Results
This study investigated an incident cohort of 64 442 patients, and 2338 patients have been prescribed clozapine. Of these, 998 patients had TRS. In survival analysis, clozapine showed a worse survival rate for psychiatric admissions than olanzapine (hazard ratio 0.615). We also identified that clinicians tended to try a number of antipsychotics, as recommended, before starting patients on clozapine.
Conclusions
In conclusion, we found that olanzapine led to higher survival rates for psychiatric admissions than clozapine. Thus, considering the risk of serious adverse effects, clozapine may be used conservatively. Considering several studies advocating superior efficacy of clozapine, further studies with extensive data are recommended.
Combination olanzapine and samidorphan (OLZ/SAM), in development for schizophrenia and bipolar I disorder, is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. OLZ/SAM safety, tolerability, and efficacy from a 52-week open-label extension study in patients with schizophrenia are reported.
Methods
Patients previously completing the 4-week, double-blind ENLIGHTEN-1 study switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Assessments included adverse events (AEs), weight, vital signs, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression-Severity (CGI-S) scores. Baseline was prior to first dose of OLZ/SAM in the extension study.
Results
In total, 281 patients enrolled, 277 received ≥1 OLZ/SAM dose, and 183 (66.1%) completed 52 weeks. Reasons for discontinuation included patient withdrawal (15.5%), loss to follow-up (6.9%), AEs (5.8%), and lack of efficacy (1.8%). AEs were reported in 136 (49.1%) patients; increased weight (13%) and somnolence (8%) were most common. Ten serious AEs were reported in eight patients (2.9%); none were considered treatment related. There were no deaths. Mean (SD) baseline weight was 79.1 (17.8) kg. Mean weight change from baseline to week 52 was 1.86 kg (2.79% increase). PANSS total and CGI-S scores continued to decline over 52 weeks (mean [95% CI] changes from baseline to week 52: −16.2 [−18.5, −14.0] and −0.9 [−1.0, −0.8], respectively).
Conclusion
OLZ/SAM was generally well tolerated in this extension study; most patients completed the 52-week treatment period with sustained improvement in schizophrenia symptoms. Mean increases in weight stabilized by week 6 with limited subsequent change through end of treatment.
Olanzapine is a novel antipsychotic agent. It has a pleotrophic pharmacology and affects dopaminergic, serotonergic, muscarinic and adrenergic activities. The therapeutic advantage of recent antipsychotics (so-called atypical antipsychotics) has been attributed to alpha-2 adrenergic antagonist effects.
Objective
The aim of this study was to evaluated effectiveness of Olanzapine in patients with schizophrenia.
Methods
Study was designed for 8-week, observational study. 40 patients, both genders, aged 20-65 years, with diagnosed various types of schizophrenia were enrolled in the study as outpatient and inpatient setting. The patients had to have a total score ≥40 on Positive and Negative scale - two parts of the Positive and Negative Syndrome Scale (PANSS). The efficacy parameter was the percent of score difference between baseline and week 8 of therapy on two above-mentioned PANSS subscales. The difference was considered as significant improvement if decrease from the baseline was 20% or more.
Results
All 40 enrolled patients completed the study. After the 8 weeks of treatment, 32/40 patients (80%) had clinically significant improvement of 20% or more decreased total PANSS score (Positive and Negative subscale). In 8/40 patients (20%) clinical improvement was also reported with < 20% decreased total PANSS score.
Conclusions
In this observational study olanzapine appears to be very good effectiveness in patients with schizophrenia.
We report the case of a patient with treatment-resistant obsessive-compulsive disorder (OCD) that had a significant reduction in obsessive-compulsive symptoms after the addition of the atypical antipsychotic to the Selective serotonin reuptake inhibitors (SSRIs)
Methods
Ms. A, a 31-year-old woman, with no family history of psychiatric disorders has been suffering from OCD for 4 years. His main obsession was contamination, and his compulsions (washing rituals) occupied 12 hours a day, rendering him unfit for work in there house or employment. Various treatments had been ineffective. His Yale-Brown Obsessive Compulsive Scale total score (Y-BOCS) at his first psychiatric interview was 38. He was taking clomipramine, sertraline, haloperidol, amisulpride, and alprazolam. Previous trials did not result in clinically meaningful responses (side effects prevented titration to higher doses), however all psychiatric drugs were discontinued except sertraline (100 mg/day) associated with olanzapine (5 mg/day).
Results
After 10 days, Ms. A reported significantly lessened anxiety and, after three months, significantly lessened obsessive-compulsive symptoms. By the fourth month, his symptoms were occurring for only few hours week Y-BOCS total score of 16). At this point, the addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients.
Conclusion
Current options for treatment-resistant OCD include switching to an alternative selective serotonin reuptake inhibitor or augmentation with other agents. Our case suggests that olanzapine may be an option for treatment-resistant OCD, but controlled studies are needed to substantiate this observation.
We report the case of a patient with treatment-resistant obsessive-compulsive disorder (OCD) that had a significant reduction in obsessive-compulsive symptoms after the addition of the atypical antipsychotic to the Selective serotonin reuptake inhibitors (SSRIs)
Methods
Ms. A, a 31-year-old woman, with no family history of psychiatric disorders has been suffering from OCD for 4 years. His main obsession was contamination, and his compulsions (washing rituals) occupied 12 hours a day, rendering him unfit for work in there house or employment. Various treatments had been ineffective. His Yale-Brown Obsessive Compulsive Scale total score (Y-BOCS) at his first psychiatric interview was 38. He was taking clomipramine, sertraline, haloperidol, amisulpride, and alprazolam. Previous trials did not result in clinically meaningful responses (side effects prevented titration to higher doses), however all psychiatric drugs were discontinued except sertraline (100 mg/day) associated with olanzapine (5 mg/day).
Results
After 10 days, Ms. A reported significantly lessened anxiety and, after three months, significantly lessened obsessive-compulsive symptoms. By the fourth month, his symptoms were occurring for only few hours week (Y-BOCS total score of 16). At this point, the addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients.
Conclusion
Current options for treatment-resistant OCD include switching to an alternative selective serotonin reuptake inhibitor or augmentation with other agents. Our case suggests that olanzapine may be an option for treatment-resistant OCD, but controlled studies are needed to substantiate this observation.
Fifty clinically stable, schizophrenic outpatients, suffering from residual schizophrenic symptoms and/or neurological side effects, were randomised to either continue their conventional neuroleptic(s) or change it to olanzapine. After 12 weeks patients on olanzapine exhibited significant improvement in neurological side effects and psychotic symptomatology as compared to patients on conventional antipsychotics.
The aim of this study was to investigate whether lower lithium levels (LoLi) or olanzapine doses (LoOL) are risk factors for future mood episodes in patients with bipolar I disorder.
Methods
A post-hoc analysis of the olanzapine-lithium-maintenance study [31] was performed using proportional hazards Cox regression models and marginal structural models (MSMs), adjusting for non-random assignments of dose during treatment.
Results
The LoLi group (< 0.6 mmol/L) had a significantly increased risk of manic/mixed (hazard ratio [HR] = 1.96, p = 0.042), but not depressive (HR = 2.11, p = 0.272) episodes, compared to the combined medium (0.6–0.79 mmol/L) and high lithium level (≥ 0.8 mmol/L) groups. There was no significant difference in risk between the two higher lithium level groups (0.6-0.79 mmol/L; ≥ 0.8 mmol/L) for new manic/mixed (HR = 0.96, p = 0.893) or depressive (HR = 0.95, p = 0.922) episodes. The LoOL group (< 10 mg/day) showed a significantly increased risk of depressive (HR = 2.24, p = 0.025) episodes compared to the higher olanzapine (HiOL) dose group (HiOL: 10–20 mg/day), while there was no statistically significant difference in risk for manic/mixed episodes between the two groups (HR = 0.94, p = 0.895).
Conclusion
Lithium levels ≥ 0.6 mmol/L and olanzapine doses ≥ 10 mg/day may be necessary for optimal protection against manic/mixed or depressive episodes, respectively in patients with bipolar I disorder.
To evaluate the safety and tolerability of olanzapine in the treatment of elderly patients with schizophrenia.
Methods
A total of 135 outpatients with schizophrenia ≥60 years of age were treated with olanzapine (n = 105) or another antipsychotic (n = 30) and followed up for 6 months. Safety measures included the recording of spontaneous adverse events and extrapyramidal symptoms (EPS). Clinical status and effectiveness of the medications were measured using the Clinical Global Impressions-Severity of Illness and the Global Assessment of Function (GAF) scales. Quality of life was assessed by means of the Spanish version of the EuroQol. The Awad scale was applied to evaluate patients’ subjective attitude towards medication.
Results
The incidence of overall adverse events and EPS was non-significantly lower in patients treated with olanzapine than in patients treated with other antipsychotics. The use of anticholinergic drugs was significantly lower (P = 0.04) in patients treated with olanzapine. Both groups of patients experienced similar improvements in Clinical Global Impressions-Severity and GAF scores. Non-significantly greater improvement in the acceptance of medication occurred at endpoint in olanzapine-treated patients than in control patients as measured by the Awad scale. The improvement in the EuroQol quality of life scale achieved at the end of study did not differ between both treatment groups.
Conclusions
Results from this naturalistic study showed that olanzapine was as safe and effective as other antipsychotic drugs in the treatment of elderly patients with schizophrenia.
To compare the efficacy and safety of amisulpride and olanzapine in subjects with schizophrenia and comorbid depression in a randomised double-blind trial.
Patients
Eighty-five adult patients fulfilling DSM-IV criteria for schizophrenia and presenting a depressive episode were randomised to amisulpride (200–600 mg/day) or olanzapine (5–15 mg/day) for 8 weeks. Primary efficacy variables were change in Calgary Depression Scale (CDS) score and Clinical Global Impression (CGI) of Change. Safety was monitored by adverse event reporting and determination of extrapyramidal function and metabolic variables.
Results
The mean change from baseline of CDS score was –6.84 in the amisulpride group and –7.36 in the olanzapine group. 65.9% and 61.5% of subjects, respectively, were considered “much” or “very much” improved. No significant inter-group difference in effect size was observed. The frequency of adverse events was low and emergence of extrapyramidal symptoms was not seen. Four patients in the olanzapine group developed abnormal triglyceride levels. Mean weight gain was 1.45 and 0.5 kg, respectively, in the olanzapine and amisulpride groups.
Conclusion
Amisulpride and olanzapine are effective in patients with schizophrenia and comorbid depression. Tolerance of both drugs was acceptable, although use of olanzapine was associated with a trend toward greater metabolic side-effects [19].
We conducted a naturalistic, multicenter, 24-hour, nonrandomized, observational study describing for the first time the effectiveness and safety of intramuscular (IM) olanzapine to control agitation and aggression in “real world” patients with psychosis. The data thus obtained was compared with that reported from randomized double-blind clinical trials.
Method
92 patients attending psychiatric emergency settings were enrolled. The study subjects were 44 male and 48 female patients with a mean age of 36.5 ± 12 years and DSM-IV-TR diagnoses of schizophrenia (48.9%), psychotic disorder not specified (23.9%) or bipolar disorder (27.2%). 10 mg IM olanzapine was administered to all patients. An optional second injection was permitted ≥ 2 hours later in line with hospital policy. Evaluations (PANSS-EC and CGI-S) were performed at baseline and 2 and 24 hours following the IM injection.
Results
Two hours after IM olanzapine was administered, a mean decrease of –9.6 in the PANSS-EC from a baseline score of 26.5 was recorded. At the 24-hour endpoint a statistically and clinically significant reduction in the PANSS-EC scores (11.6 ± 5.3) was observed as compared with values at study entry (26.5 ± 5.9) and at 2 hours endpoint (16.9 ± 9.3), which represent a mean decrease of –14.9 and –5.3, respectively.
Conclusion
The present naturalistic study provides naturalistic data on the effectiveness of IM olanzapine in the treatment of acute agitation in patients with schizophrenia or bipolar mania that is in line the data obtained in randomized double-blind clinical trials.
There are few controlled studies evaluating the treatment of bipolar mixed states. Evidence suggests that mixed states may be more responsive to some anticonvulsants than to lithium. Olanzapine alone or in combination with divalproate or lithium has been adequately evaluated in randomized clinical trials involving mixed-state patients, whereas risperidone and quetiapine have not. There is also some evidence demonstrating the efficacy of ziprasidone and aripiprazole. The risk of switching to depression is high in mixed states. Conventional antipsychotics, such as haloperidol, may be less efficacious at protecting against a switch to depression than atypical antipsychotics, divalproate or lithium. When choosing drugs for the treatment of mania, and especially for the treatment of mixed states, their efficacy against manic and depressive symptoms, and their safety in terms of the risk of switching to depression should be taken into account.
The aim of this study was to explore the treatment effect of olanzapine in the polymorphisms of MAOA and DRD4 VNTRS in schizophrenia.
Method:
Over a 3-month period, 50 patients with schizophrenia were administered olanzapine (10–30mg). Treatment response was assessed by checking for improvement in psychotic symptoms as measured on the Positive and Negative Syndrome Scale Manual (PANSS Manual) and Brief Psychiatric Rating Scale (BPRS).
Results:
The long form of MAOA demonstrated a better drug response for positive symptoms, and the short form of MAOA demonstrated a better drug response for aggression. There was a negative correlation between DRD4 VNTRS and improvement in general psychopathology. Both female patients and those with a shorter duration of the illness had a better response to olanzapine.
Conclusion:
The results suggest polymorphisms of MAOA and the DRD4 gene, sex, and duration of illness may be useful response predictors in schizophrenia.