Zvi Zemishlany

Sexual Dysfunction in Male Posttraumatic Stress Disorder Patients

Background: Previous studies have suggested that sexual dysfunction may be associated with posttraumatic stress disorder (PTSD). Yet such studies have not examined a full range of sexual functioning and have not accounted for the possibility that medication used to treat PTSD may contribute to sexual dysfunction. Objective: The current study compares the various components of sexual functioning among three groups of males: (1) untreated PTSD patients (n = 15), (2) PTSD patients currently treated with selective serotonin reuptake inhibitor (SSRI) agents (n = 27) and (3) a group of normal controls (n = 49). Methods: All participants completed an 18-item questionnaire for assessment of sexual functioning. Those with PTSD also completed the Impact of Events Scale and the Symptom Check List-90 (SCL-90). Results: Untreated and treated PTSD patients had significantly poorer sexual functioning in all domains (desire, arousal, orgasm, activity and satisfaction) as compared to normal controls. Those treated with SSRI had greater impairment in desire, arousal and frequency of sexual activity with a partner. There was a high correlation between sexual dysfunction among the PTSD group and the anger-hostility subscale of the SCL-90. Conclusions: PTSD appears to be associated with pervasive sexual dysfunction that is exacerbated by treatment with SSRIs. PTSD may represent a heterogeneous syndrome. Patients with PTSD have a high rate of comorbid panic disorder, major depression and anxiety, and it could thus be argued that these comorbid disorders, rather than PTSD, accounted for the observed result. Future research aimed at understanding comorbidity and heterogeneity should help to illuminate the psychobiology of PTSD and eventually guide both medication and psychosocial treatments.

4-Aminopyridine in the treatment of Alzheimer's disease.

The cognitive and behavioral effect of 4-aminopyridine (4-AP) was examined in Alzheimers disease (AD) using a dose finding/replication study design. Fourteen inpatients, aged 54-89 years (mean 66.1 +/- 10.6 SD), meeting NINCDS criteria for probable AD, were studied. Three doses of 4-AP--2.5 mg b.i.d., 5 mg b.i.d., and 10 mg b.i.d.--or placebo were administered for 4 consecutive days in random order. Symptomatic assessment was performed on the fourth day of each condition using the Alzheimer Disease Assessment Scale (ADAS). Thereafter, the dose on which the best performance occurred was readministered, as was placebo. Of the 13 patients who completed the dose-finding phase, 7 patients had at least one dose of 4-AP that was associated with less severe symptoms than was placebo, and those patients were included in the replication phase. Results indicated no significant difference in total ADAS scores (p greater than 0.05). Examination of the ADAS subscales revealed no significant 4-AP effect on any particular symptom. Possible explanations of the lack of a drug effect in this study include the unselective release of neurotransmitters by 4-AP, poor penetration into the central nervous system (CNS), and the presenile onset of the disease in these patients.

Reliability of post-mortem chart diagnoses of schizophrenia and dementia

The reliability of psychiatric diagnosis has a direct effect on the validity of post-mortem analyses of neuropathological data, yet little is known about the reliability of retrospective diagnostic procedures which rely on review of medical records. In this paper, we report on the reliability of DSM-III-R psychiatric diagnoses assigned by a pool of 8 raters to a set of 106 state hospital charts of elderly, chronic patients who had died while institutionalized and were autopsied. Diagnoses were grouped by general diagnostic class, and Kappa coefficients computed for agreement among raters, as well as for agreement between ultimate consensus diagnoses and those made while subjects were living. Interrater agreement for those diagnoses that occurred most frequently in this sample (e.g. Schizophrenia and Dementia) was excellent, and comparable to the the agreement observed for ratings of live patients. Interrater agreement for less frequently occurring diagnoses (e.g. Mental Retardation, Mood Disorders, other non-Schizophrenic Psychoses) ranged from excellent to poor. We found high agreement between our rates diagnoses and those assigned by state hospital personnel while patients were living, although post-mortem review produced lower rates of diagnosis of both schizophrenia and Alzheimer-type dementias. Overall, results suggest that the reliability of chart review diagnosis is comparable to that obtained from interviews of live patients when experienced raters are used and diagnostic base rates are high enough to produce stable estimates of reliability.

Selegiline in the treatment of sexual dysfunction in schizophrenic patients maintained on neuroleptics: a pilot study.

A double-blind, placebo-controlled crossover study was undertaken in 10 neuroleptic-treated male schizophrenic outpatients to assess the effect of coadministration of selegiline 15 mg/day for 3 weeks on their sexual dysfunction. Selegiline was not found to be effective in improving any domain of sexual functioning despite a significant decrease in prolactin levels (P < 0.05). This study emphasizes the complex nature of sexual dysfunction in schizophrenic-treated patients and the need for placebo-controlled trials for this condition.

Acute effects of haloperidol on cerebral cortex blood flow in normal and schizophrenic subjects

To evaluate the effects of neuroleptic medications on cerebral blood flow (CBF), cortical perfusion was quantified by the 133xenon technique in 8 unmedicated schizophrenics and 9 healthy controls before, and 1 and 3 hours after, administration of haloperidol (5 mg per os). At 3 hours, the normal subjects, but not schizophrenic patients, showed a significant increase in global mean perfusion (17 +/- 13%). Changes in CBF were not associated with plasma haloperidol levels or the presence of extrapyramidal side effects, and remained significant after controlling for pCO2. The lack of change in CBF in schizophrenic patients following acute haloperidol administration may be due to prior neuroleptic exposure, absence of anxiety, or other nonspecific factors, or may reflect a more fundamental feature of underlying pathophysiology in schizophrenia.

Sildenafil citrate for the sexual dysfunction in antidepressant-treated male patients with posttraumatic stress disorder. A preliminary pilot open-label study.

Background: Previous studies have suggested that posttraumatic stress disorder (PTSD) may be associated with pervasive sexual dysfunction. Sildenafil citrate was established as a highly effective and well-tolerated oral agent for the treatment of sexual dysfunction of various etiologies. There are no studies that have examined the efficacy of oral sildenafil in PTSD patients with sexual dysfunction. Objective: The current study evaluated the impact of sildenafil added to an ongoing antidepressive treatment in male PTSD patients. Methods: Ten consecutive male PTSD patients who complained of sexual dysfunction were enrolled in an open-label 4-week fixed-dose study of sildenafil citrate 50 mg/day p.r.n. Patients were evaluated at baseline and after treatment with the Clinician-Administered PTSD Scale (CAPS); sexual function assessments were performed using the International Index of Erectile Function. Results: All patients completed the study and statistically significant improvement was observed in all evaluated domains of sexual functioning: erectile function (53.5%), orgasmic function (40.3%), sexual desire (53%), intercourse satisfaction (82%) and overall satisfaction (57.4%). Oral sildenafil treatment appeared to be well tolerated and no single patient stopped the treatment. Improvements in various CAPS subscales were also obtained; however, there was no significant correlation between improvement in sexual functioning and the changes in CAPS subscale scores. Conclusion: Sildenafil seems to be an efficacious, safe and well-tolerated treatment of sexual dysfunction in antidepressant-treated male PTSD patients.

Effectiveness and safety of citalopram in hospitalized adolescents with major depression: a preliminary, 8-week, fixed-dose, open-label, prospective study.

Objective:Citalopram is widely used in adolescents with major depressive disorder (MDD) and anxiety; however, data on efficacy and safety are still limited and inconsistent. The aim of this study was to evaluate both the efficacy and the safety of citalopram for treatment of MDD and anxiety symptoms in adolescent inpatients. Methods:An open-label, prospective design of an 8-week trial with a fixed dose of 20 mg/d of citalopram was performed in 10 hospitalized adolescents. Clinical state was assessed by Hamilton Depression (HAM-D 17) and Hamilton Anxiety scales, Beck Depression Inventory (BDI), and the Clinical Global Impression-Severity Scale for depression. Suicidal risk was assessed by the Suicide Risk Scale. A 30% improvement in the rating scales was considered as being a response to the treatment. Results:After 8 weeks, depression levels as measured by the HAM-D 17 (P = 0.002), the BDI (P = 0.011), and the Clinical Global Impression-Severity Scale (P = 0.002) showed significant improvement. So did anxiety levels, as measured by the Hamilton Anxiety (P = 0.026) at end point. Subjective depression level (BDI) decreased significantly between week 2 and 4 (Z = −2.36, P = 0.018), whereas objective depression level (HAM-D 17) decreased significantly between week 4 and 6 (Z = −2.53, P = 0.012). Suicide risk, as assessed by the Suicide Risk Scale, however, increased significantly after 8 weeks (P = 0.011). Conclusions:This pilot small-scale trial found that citalopram was effective for both depressive and anxiety symptoms in adolescents with MDD and that response started as early as the second week. However, suicidal risk was elevated for some of the subjects. Larger randomized placebo-controlled trials are needed.