olanzapine and Stress-Disorders--Post-Traumatic

Posttraumatic stress disorder (PTSD) is a prevalent and disabling mental illness. Small studies found atypical antipsychotics (AAs) to be beneficial in the treatment of patients with PTSD regardless of psychotic symptoms who are unresponsive to conventional pharmacological treatments such as serotonin selective reuptake inhibitors. This study reports the results of a meta-analysis of existing randomized, double-blind, placebo-controlled clinical trials (RCTs) of AAs as a monotherapy or augmentation therapy for the treatment of patients with PTSD. Seven RCTs were identified through extensive scans of databases, which included PubMed, MedLine, the National PTSD Center Pilots database, PsycINFO, Cochrane Central Register of Controlled Trials, and the Abstracts Library of the American Psychiatric Association with predefined inclusion criteria. Dichotomous and continuous measures were performed using a fixed effects model, heterogeneity was assessed, and subgroup analyses were done. Data from seven RCTs involving a total of 192 PTSD patients (102 randomized to AAs and 90 randomized to placebo) were analyzed. The results show that AAs may have a beneficial effect in the treatment of PTSD, as indicated by the changes from baseline in Clinician Administered PTSD Scale total scores [standardized mean difference (SMD)=-0.45, 95% confidence interval (CI) (-0.75, -0.14), P=0.004]. In addition, the overall SMD of the mean changes in the three Clinician Administered PTSD Scale subscores was statistically significant (P=0.007) between AAs and placebo groups, favoring AAs over placebo (SMD=-0.27, 95% CI=-0.47, -0.07). In particular, the symptom of 'intrusion' was mainly responsible for this significance. Clinical significance of the results, however, should be carefully interpreted and translated into clinical practice, given that the quality and availability of currently existing RCTs included in the analysis.

Topics: Antipsychotic Agents; Benzodiazepines; Data Interpretation, Statistical; Double-Blind Method; Humans; Olanzapine; Placebos; Randomized Controlled Trials as Topic; Risperidone; Stress Disorders, Post-Traumatic

In this narrative review, we aimed to describe different pharmacological strategies for the treatment of patients with post-traumatic stress disorder who display different levels of intolerance, resistance, refractoriness, or who are unable to take to antidepressants, especially serotonin reuptake inhibitors.. We searched the ISI web of science and the PubMed for original studies focusing in the treatment of PTSD in different clinical scenarios.. Preliminary evidence pointed towards the efficacy of drugs such as risperidone, olanzapine, lamotrigine and prazosin as strategies to be employed in the above mentioned clinical scenarios. The choice of a specific "second line" drug should take into account not only symptoms, but also pattern of comorbidities, previous response to other treatments, pharmacological interactions, side-effects, and patient's physical conditions.. Future randomized controlled trials should be performed in order to unveil which drugs should be prescribed in the absence of adequate treatment and response to serotonin reuptake inhibitors.

Topics: Adrenergic Antagonists; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Humans; Lamotrigine; Olanzapine; Prazosin; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic; Treatment Failure; Triazines

Sleep disorders, such as insomnia and nightmares, are common problems in post-traumatic stress disorder (PTSD), exert a strong negative influence on the quality of life and are a great challenge for clinical psychiatry. Several studies have reported on the efficacy of drugs for the treatment of PTSD-related sleep disorders. These studies have not been systematically reviewed. This is the first review on the effectiveness of sleep medication in PTSD. We performed a Medline, EMBASE and Cochrane Library Indexed search, using the keywords: PTSD, pharmacotherapy, therapy, sleep, nightmares, insomnia and review. From this database, English-language, human subject, data driven papers published after 1980 were selected. Forty eight articles are discussed. Open-label and case studies suggest efficacy for some antidepressants, anticonvulsants and atypical antipsychotics. Only a few placebo-controlled studies have been published. They show promising results for the atypical antipsychotic olanzapine, and the alpha1-adrenoceptor antagonist prazosin. In comparison to the incidence and impact of sleep complaints in PTSD, the pharmacotherapeutic armamentarium for PTSD-related sleep complaints remains poorly investigated. Some recent studies show promising results, especially for alpha1-adrenoceptor and 5-HT2 receptor antagonists. However, randomized controlled trials with larger populations need to be conducted.

Topics: Adrenergic alpha-1 Receptor Antagonists; Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Humans; Monoamine Oxidase Inhibitors; Olanzapine; Prazosin; Selective Serotonin Reuptake Inhibitors; Sleep Wake Disorders; Stress Disorders, Post-Traumatic

Antidepressant medications have eased the suffering of millions of people. In addition to treating depression, antidepressant drugs also treat several anxiety disorders. Unfortunately, there are problematic limitations with antidepressant agents, including a delayed therapeutic response and insufficient efficacy. Emerging evidence shows that atypical antipsychotic agents can be used as augmentation therapy in patients with poor responses to antidepressants. Future drugs combining key features of antidepressant and atypical antipsychotic agents could offer new promise for patients suffering from obsessive-compulsive disorder, post-traumatic stress disorder, panic disorder, generalized anxiety disorder and depression.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Depressive Disorder, Major; Dibenzothiazepines; Drug Design; Drug Synergism; Drug Therapy, Combination; Humans; Obsessive-Compulsive Disorder; Olanzapine; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Histamine; Receptors, Serotonin; Risperidone; Stress Disorders, Post-Traumatic

Although there have been important advances in the treatment of posttraumatic stress disorder (PTSD), many patients fail to respond to first-line pharmacotherapy. Limited evidence suggests that second generation antipsychotics may have a role to play as monotherapy in PTSD.. We undertook a randomized, placebo-controlled study using flexible-dose olanzapine monotherapy for 8 weeks in 28 adult male and female participants (mean age: 40.75 ± 11.59 years) with non-combat related chronic PTSD. Data were analysed with repeated measures analysis of variance, using an intention to treat, last observation carried forward approach.. The olanzapine group (n = 14) demonstrated significantly greater improvement on the Clinician Administered PTSD Scale from baseline to endpoint than the placebo group (n = 14) (F = 5.71, p = 0.018). Olanzapine was generally well tolerated, with no serious adverse events recorded. Substantial weight gain (6-10 kg) was, however, reported in 6/14 participants in the olanzapine group.. To our knowledge, this is the first controlled evidence of the efficacy of olanzapine monotherapy in an exclusively non-combat related chronic PTSD group. Despite the small sample size, these data suggest that olanzapine may have a role in the treatment of PTSD. These findings warrant replication in a larger sample.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Stress Disorders, Post-Traumatic; Treatment Outcome; Weight Gain

Combat-related post-traumatic stress disorder (PTSD) is often complicated with other psychiatric comorbidities, and is refractory to treatment.. The aim of an open, comparative 6-week study was to compare olanzapine and fluphenazine, as a monotherapy, for treating psychotic combat-related PTSD.. Fifty-five male war veterans with psychotic PTSD (DSM-IV criteria) were treated for 6 weeks with olanzapine (n=28) or fluphenazine (n=27) in a 5-10 mg/day dose range, once or twice daily. Patients were evaluated at baseline, and after 3 and 6 weeks of treatment, using Watson's PTSD scale, Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity Scale (CGI-S), Clinical Global Impression Improvement Scale (CGI-I), Patient Global Impression Improvement Scale (PGI-I) and Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS).. At baseline, patient's data (age, duration of combat experience and scores in all measurement instruments) did not differ. After 3 and 6 weeks of treatment, olanzapine was significantly more efficacious than fluphenazine in reducing symptoms in PANSS (negative, general psychopathology subscale, supplementary items), Watson's PTSD (avoidance, increased arousal) subscales, CGI-S, CGI-I, and PGI-I scale. Both treatments affected similarly the symptoms listed in PANSS positive and Watson's trauma re-experiencing subscales. Fluphenazine induced more extrapyramidal symptoms. Prolongation of the treatment for 3 additional weeks did not affect the efficacy of either drug.. Our data indicate that both fluphenazine and olanzapine were effective for particular symptom profile in psychotic combat-related PTSD. Olanzapine was better than fluphenazine in reducing most of the psychotic and PTSD symptoms, and was better tolerated in psychotic PTSD patients.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dose-Response Relationship, Drug; Fluphenazine; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Stress Disorders, Post-Traumatic

Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder (PTSD) symptoms, we conducted a 10-week, double-blind, placebo-controlled evaluation in which 15 patients were randomized 2:1 to either olanzapine or placebo. The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day. Eleven patients completed the study. Patients in both groups showed improvement in PTSD symptoms, but no between-group differences in treatment response were observed and a high placebo response rate was found. Both treatments were tolerated well, although the olanzapine treatment group had more weight gain. Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD. The lack of difference between olanzapine and placebo may in part be due to olanzapine's not being effective in PTSD or, alternatively, a small sample size, a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients.

Topics: Adolescent; Adult; Aged; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Pilot Projects; Pirenzepine; Stress Disorders, Post-Traumatic; Treatment Outcome

Post-traumatic stress disorder (PTSD) is a common and increasingly diagnosed mental illness. Recent pharmacotherapeutic research on treatments for this condition has focused on antidepressant drugs with serotonergic actions. However, the presence of intrusive, psychotic-like symptoms in a substantial portion of PTSD patients raises the possibility that antipsychotics with serotonergic properties might also prove useful in treating PTSD. We conducted an open-label 8-week study of olanzapine treatment in veterans with combat-induced PTSD. Primary outcome measures in this study were the Clinician Administered PTSD Scale (CAPS) and the Clinical Global Impressions Improvement scale. Secondary outcome measures included the Hamilton Rating Scales for Depression (HRSD) and Anxiety (HRSA). Forty-eight patients enrolled in the study, and 30 completed the 8-week trial. Results of intent-to-treat and completer analyses demonstrated that all outcome measures improved significantly during treatment. Secondary analyses indicate that improvement in the intrusive symptom cluster of the CAPS was independent of improvement on the HRSD and HRSA. In conclusion, the study indicates that olanzapine treatment is useful in alleviating the symptoms of combat-induced PTSD.

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Stress Disorders, Post-Traumatic; Time Factors; Treatment Outcome

Topics: Adult; Adult Survivors of Child Abuse; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Desvenlafaxine Succinate; Eye Movement Desensitization Reprocessing; Female; Humans; Olanzapine; Paranoid Disorders; Psychotic Disorders; Stress Disorders, Post-Traumatic

Topics: Adolescent; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Humans; Intellectual Disability; Male; Olanzapine; Stress Disorders, Post-Traumatic; Vitamin E

Post Traumatic Stress Disorder is an anxiety disorder with prolonged distortion of rational behavior. In this study, we report the preclinical potential of olanzapine (OLZ) in the treatment of PTSD. Since the atypical antipsychotics have modulating effects on cell protective and destructive factors, we tested the effects of OLZ in PTSD regarding these cell modulating factors. Rats, when subjected to stress-restress (SRS) model of PTSD, showed a derangement in cell protective factors like the decline in BDNF, ERK, and CREB. While the adversarial factors like caspase-3 were enhanced. Four weeks treatment with OLZ at doses of 1 and 10 mg/kg significantly mitigated the SRS-induced derangement related to PTSD. OLZ at doses of 1 and 10 mg/kg enhanced BDNF, ERK and CREB levels which were reduced by SRS in PTSD animals. Further, at the fore mentioned doses it also inhibited the elevation of caspase-3 a downstream apoptotic factor. Besides, OLZ also showed mitigation in behavioral alterations related to anxiety and memory brought about by PTSD. These effects of OLZ were comparable to that of paroxetine a clinically approved drug for PTSD in terms of biochemical and behavioral assessments indicating its anti-PTSD potential.

Topics: Animals; Brain-Derived Neurotrophic Factor; Caspase 3; Cyclic AMP Response Element-Binding Protein; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases; Male; Olanzapine; Psychotropic Drugs; Random Allocation; Rats; Signal Transduction; Stress Disorders, Post-Traumatic

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain Injuries; Humans; Male; Olanzapine; Radiography; Stress Disorders, Post-Traumatic; Tomography Scanners, X-Ray Computed

Huntington's disease (HD) is a neurodegenerative, autosomal dominant disease that manifests with a triad of symptom clusters including movement disorder, cognitive impairment and psychiatric symptoms. We present a patient with HD who, prior to developing neurological signs and symptoms, had been exposed to war trauma and had developed posttraumatic stress disorder. Fifteen years later he manifested with dysarthria, difficulties with swallowing and involuntary movement. What brought him to psychiatrist was a heteroanamnestically noticed change in personality with irritable mood, impulsivity, aggressive outbursts in behavior and delusional ideation. Therapy was stared with haloperidol, but patient developed severe extrapiramidal side effects. Subsequent treatment with olanzapine, diazepam and omega 3 fatty acids lead to mood stabilization and better impulse control with even some improvement in motoric symptoms. To our knowledge, this is the first case report on combat related PTSD as psychiatric disorder manifested prior to HD. We discuss a possible influence of psychological stress disorder on severity of psychiatric symptoms in the HD. The importance of personalized approach in both psychopharmacological and psychotherapeutical treatment of patients with HD is emphasized. If the influence of environmental stress on the psychiatric phenotype of the disease should be confirmed by clinical trials and further studies, both screening methods and interventions aimed to reduce psychological stress in carriers of Huntington gene could be considered.

Topics: Alleles; Antipsychotic Agents; Atrophy; Benzodiazepines; Cerebral Cortex; Chromosomes, Human, Pair 4; Combat Disorders; Combined Modality Therapy; Comorbidity; Diagnosis, Differential; Diazepam; Fatty Acids, Omega-3; Genetic Testing; Humans; Huntington Disease; Magnetic Resonance Imaging; Male; Medulla Oblongata; Middle Aged; Neurologic Examination; Olanzapine; Patient Care Team; Psychotherapy; Risk Factors; Social Environment; Stress Disorders, Post-Traumatic; Trinucleotide Repeats

A 38-year-old woman with medication-resistant major depression and posttraumatic stress disorder was treated with electroconvulsive therapy (ECT) concurrent with a duloxetine-olanzapine combination. The treatment resulted in complete resolution of major depression without any complications. This case report suggests that treatment with the combination of duloxetine and olanzapine concurrently with ECT was found safe and uncomplicated. The literature on the combined use of antidepressants and ECT is briefly reviewed.

Topics: Adult; Benzodiazepines; Combined Modality Therapy; Depressive Disorder, Major; Duloxetine Hydrochloride; Electroconvulsive Therapy; Female; Humans; Olanzapine; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic; Thiophenes

Nightmares and insomnia in combat-related post-traumatic stress disorder (PTSD) might be resistant to treatment with selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines.. We describe five case reports of patients suffering from long-lasting and intractable nightmares and insomnia. They were given different psychotropic agents in past few years, with no improvement in their sleep disturbance. Olanzapine was added to the current treatment regimen.. Both nightmares and insomnia improved rapidly after olanzapine institution in all of five patients. No adverse events of olanzapine were reported.. Olanzapine augmentation might be useful in alleviating treatment-resistant nightmares and insomnia in patients with combat-related PTSD.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Combat Disorders; Dose-Response Relationship, Drug; Dreams; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors; Sleep Initiation and Maintenance Disorders; Stress Disorders, Post-Traumatic; Time Factors; Treatment Outcome; Warfare

To report a case of olanzapine-induced hyperglycemia leading to a hyperosmolar, hyperglycemic, nonketonic coma.. A 51-year-old, 85.5-kg (ideal body weight 79.9 kg), white man presented to a Veterans Affairs hospital with a serum glucose concentration of 1596 mg/dL. Soon thereafter, he went into a hyperosmolar, hyperglycemic, nonketonic coma. Olanzapine therapy had been instituted less than six months prior to this event; approximately two months before this event, his blood glucose was 108 mg/dL. Eight days after stopping olanzapine, the glucose concentration returned to normal, and the patient no longer required insulin nor any other glucose-lowering agents.. The insulin resistance caused by olanzapine is normally attributed to the weight gain associated with the drug. In this patient, it appears that olanzapine caused hyperglycemia by a mechanism other than weight gain.. This case report and others from the literature suggest that olanzapine therapy may induce hyperglycemia in some patients.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Male; Middle Aged; Olanzapine; Pirenzepine; Stress Disorders, Post-Traumatic

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Stress Disorders, Post-Traumatic; Treatment Outcome