Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) can be a chronic and disabling condition. Post-traumatic nightmares (PTNs) form a core component of PTSD and are highly prevalent in this patient population. Nightmares in PTSD have been associated with significant distress, functional impairment, poor health outcomes, and decreased quality of life. Nightmares in PTSD are also an independent risk factor for suicide. Nightmare cessation can lead to improved quality of life, fewer hospital admissions, lower healthcare costs, and reduced all-cause mortality. Effective treatment of nightmares is critical and often leads to improvement of other PTSD symptomatology. However, approved pharmacological agents for the treatment of PTSD have modest effects on sleep and nightmares, and may cause adverse effects. No pharmacological agent has been approved specifically for the treatment of PTNs, but multiple agents have been studied. This current narrative review aimed to critically appraise proven as well as novel pharmacological agents used in the treatment of PTNs. Evidence of varying quality exists for the use of prazosin, doxazosin, clonidine, tricyclic antidepressants, trazodone, mirtazapine, atypical antipsychotics (especially risperidone, olanzapine and quetiapine), gabapentin, topiramate, and cyproheptadine. Evidence does not support the use of venlafaxine, ß-blockers, benzodiazepines, or sedative hypnotics. Novel agents such as ramelteon, cannabinoids, ketamine, psychedelic agents, and trihexyphenidyl have shown promising results. Large randomized controlled trials (RCTs) are needed to evaluate the use of these novel agents. Future research directions are identified to optimize the treatment of nightmares in patients with PTSD.

Clozapine-Associated Leukopenia and Agranulocytosis in Western Cape, South Africa: A 3-Year Retrospective Cohort Study.

BACKGROUND: Clozapine may cause life-threatening hematological side effects (HSEs). Hematological side effect incidence data from Sub-Saharan Africa are lacking. Furthermore, clozapine reduces cellular immunity, and it is unknown whether clozapine is a risk factor for tuberculosis or whether HIV is a risk factor for developing HSEs. We assessed the incidence of HSEs in South Africans from the Western Cape Province on clozapine, and the secondary objective was to determine the association of HIV and tuberculosis with clozapine exposure. METHODS: We conducted a 24-week retrospective descriptive study of patients initiated on clozapine between January 2015 and December 2017 using anonymized data from the Provincial Health Data Centre. A control group of patients initiated on risperidone was selected. RESULTS: We identified 23,328 patients and included 5213 who had white blood cell monitoring (n = 1047 clozapine, n = 4166 risperidone). The incidence of leukopenia in patients on clozapine was 0.38% (95% confidence interval [CI], 0.01%-0.76%) measured over a 24-week period and was 0.41% in patients on risperidone (95% CI, 0.21%-0.6%) (P = 0.91). The incidence of agranulocytosis in patients on clozapine was 0.19% (95% CI, 0.00%-0.46%) measured over a 24-week period and was 0.24% in patients on risperidone (95% CI, 0.09%-0.39%) (P = 0.266). HIV-infected patients had a 7.46 times increased risk of developing leukopenia (95% CI, 3.37-16.48; P < 0.01). Patients who developed leukopenia had a 6.24 times increased risk of contracting tuberculosis (95% CI, 1.84-21.11; P < 0.01). CONCLUSIONS: Our incidence of clozapine-induced HSEs was lower than previously reported and not significantly different compared with risperidone. HIV infection was associated with HSEs. Patients with HSEs had an increased risk of developing tuberculosis.