Sexual side-effects of contemporary antidepressants: review.

The aim of the present study was to review the sexual side-effects of contemporary antidepressants in Australia, comparing the selective serotonin re-uptake inhibitors (SSRIs) with venlafaxine, reboxetine, mirtazepine, duloxetine, bupropion, desvenlafaxine and agomelatine. Double-blind, randomized comparative studies of these antidepressants that included assessment of sexual dysfunction with validated rating scales in patients with major depressive disorder were identified from the literature using MEDLINE, EMBASE and PsychINFO databases. Bupropion and duloxetine caused significantly less sexual dysfunction than the SSRIs in short-term studies and reboxetine significantly less in both short- and longer term studies. Bupropion and agomelatine caused significantly less sexual dysfunction than venlafaxine. The evidence for mirtazepine having an advantage over the SSRIs is lacking and there are currently insufficient data for desvenlafaxine. Well-designed comparative studies of contemporary antidepressants with direct assessment of sexual side-effects as the primary outcome measure are scarce. Future studies should be randomized, double-blind, active controlled trials in sexually active subjects with major depressive disorder. There should be direct assessment of sexual function and depression using reliable, validated rating scales before and during treatment. Studies should assess treatment-emergent effects in patients with normal function and resolution of baseline dysfunction over treatment, in both the short and long term. Further research should compare available instruments for measuring sexual function, and include separate analyses of both remitters/non-remitters and male/female subjects.

Blunted growth hormone response to clonidine in post-traumatic stress disorder.

Hyperactivity of the sympathetic and noradrenergic systems is thought to be a feature of post-traumatic stress disorder (PTSD). Assessment of noradrenergic receptor function can be undertaken by measuring the growth hormone (GH) response to the alpha2-agonist clonidine. The aim of this study was to examine whether subjects with combat-related PTSD (with or without co-morbid depression) have a blunted growth hormone response to clonidine, compared to a combat-exposed control group. Twenty-three Vietnam veterans suffering from PTSD alone, 27 suffering from PTSD and co-morbid depression, and 32 veteran controls with no psychiatric illness were administered 1.5 microg/kg clonidine i.v. Plasma growth hormone was measured every 20 min for 120 min. The growth hormone response to clonidine was significantly blunted in the non-depressed PTSD group compared to both the depressed PTSD group and the control group as measured by peak growth hormone, delta growth hormone and AUC growth hormone. Subjects with PTSD and no co-morbid depressive illness show a blunted growth hormone response to clonidine. This suggests that post-synaptic alpha2-receptors are subsensitive. This finding is consistent with other studies showing increased noradrenergic activity in PTSD.

Blunted prolactin response to D-fenfluramine in post-stroke major depression.

BACKGROUND: This study investigated whether patients suffering from post-stroke depressive disorder had a similar disturbance in central serotonergic function to that described in non-brain injured depressed patients. METHODS: Twenty-three depressed patients (nine major, 14 minor) and 38 non-depressed patients were examined 4-8 weeks post-stroke with a structured interview, rating scales and MRI brain scans. Patients were administered 30 mg D-fenfluramine orally and plasma prolactin and D-fenfluramine concentrations were measured for 6 h post-dose. RESULTS: The prolactin response was significantly blunted in major depression compared to minor depression and non-depressed patients as measured by both delta prolactin and area under the prolactin versus time curve. There was no significant relationship between prolactin response and lesion lateralization or any of the measured clinical characteristics. LIMITATIONS: The major limitation of the study is the relatively small number in each depressive group. CONCLUSIONS: Patients suffering from major depression in the post-stroke period have a blunted prolactin response to D-fenfluramine. This indicates a serotonergic abnormality consistent with that found in major depression where neurological disease is not present.

Sertraline in paired blood plasma and breast-milk samples from nursing mothers.

Paired blood and breast-milk samples were collected from 10 nursing mothers receiving sertraline. Samples were collected at steady state when the patients had been taking stable doses of 50-150 mg/day over several weeks. Sertraline concentrations in both fluids were determined using a specific, validated HPLC method. Plasma and milk concentrations showed a wide inter-individual variability for the same dose. Mean plasma concentrations were linearly related to dose, but this was not the case for breast-milk concentrations. An overall milk to plasma ratio of 1.76+/-1.72 was recorded. The average dose to the infants ranged from 1.1 to 31.1 &mgr;g/kg, which is less than 2 per cent of the maternal dose per day. Further studies are necessary to determine if these doses are detrimental to the development of the infant. Copyright 2000 John Wiley & Sons, Ltd.

Aripiprazole as augmentation therapy in bipolar patients with current minor or subsyndromal mood symptoms.

BACKGROUND: This study aims to evaluate the effectiveness of aripiprazole augmentation of maintenance treatment for bipolar disorder in patients with minor or subsyndromal mood episodes while on a stable dose of a mood stabiliser and/or antidepressant. METHODS: All subjects had a diagnosis of bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders-4th Edition, Text Revision). Open-label aripiprazole was given over 8 weeks initially. The starting dose was 5 to 15 mg/day with a mean final dose of 11.5 mg (±4.6). Patients were assessed at weeks 0, 2, 4 and 8 with the Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Clinical Global Impression of Severity (CGI-S). RESULTS AND DISCUSSION: Seventeen of 20 (85%) patients completed week 4, while 14 (70%) patients completed 8 weeks. For intention-to-treat data, there was a significant decrease in MADRS scores over the course of treatment, with a reduction of 6.40 points at endpoint (p < 0.0005). Improvement from baseline was significant at week 2 and remained through to week 8. Similarly, CGI-S scores significantly decreased over the course of study, but not YMRS scores. Aripiprazole was shown to be a modestly effective augmentation therapy for depressive symptoms in bipolar I and II in this small open-label study.

Prolactin response to d-fenfluramine in combat-related post-traumatic stress disorder.

Central serotonergic function can be investigated by measuring the prolactin response to the serotonin releasing/uptake agent, d-fenfluramine. This study investigated the effect of diagnosis, depressive symptoms and history of alcohol or tobacco abuse or dependence on the d-fenfluramine test in combat-related post-traumatic stress disorder (PTSD). Male, non-hospitalized combat-exposed veterans diagnosed with PTSD (DSM-III-R) and a similarly aged combat-exposed control group were assessed for both PTSD and depressive symptoms and prolactin responses to a 30-mg d-fenfluramine challenge test. Ninety-five subjects were studied; 23 were controls, 46 subjects met the criteria for current PTSD and 26 for past PTSD. There were no significant differences between the three groups for baseline prolactin, peak prolactin, and time to reach peak, delta prolactin or area under the curve of the prolactin vs. time curve. Depressive symptoms and history of alcohol or tobacco abuse or dependence did not have a confounding effect on the prolactin responses to d-fenfluramine. This study suggests that a blunted prolactin response to d-fenfluramine may be a consequence of combat exposure rather than PTSD. To confirm this, further studies involving both healthy and combat-exposed control groups in addition to subjects with PTSD of similar ages are required.