Hyponatraemia in elderly psychiatric patients treated with Selective Serotonin Reuptake Inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit

OBJECTIVE: To determine the prevalence of hyponatraemia associated with selective serotonin reuptake inhibitor (SSRI) and venlafaxine use in elderly patients compared to that in elderly patients not prescribed these drugs, while controlling for age, sex, depression status and illnesses or prescribed medications also associated with hyponatraemia. Design and setting Retrospective controlled analysis in a 36-bed inpatient unit for elderly psychiatric patients in Melbourne. PATIENTS: Inpatients (199) with a mean age of 74.2 years of whom 74 were prescribed an SSRI or venlafaxine. RESULTS: Patients on SSRIs or venlafaxine were 5.6 times as likely as patients not so treated to have hyponatraemia. Thirty-nine percent of patients on an SSRI or venlafaxine had hyponatraemia compared with 10% of controls. Ten of the 14 patients on venlafaxine were hyponatraemic. Controlling for thiazide status did not reduce the odds of these patients having hyponatraemia and taking an SSRI or venlafaxine was still strongly associated with hyponatraemia after also controlling for age, sex, and depression status, consumption of other drugs potentially causative of hyponatraemia and medical illness severity (Odds Ratio (OR) 3.5, p = 0.008). CONCLUSIONS: SSRI and venlafaxine use is strongly associated with the presence of hyponatraemia in a population of elderly psychiatric inpatients and the association is not due to confounding by age, sex, depression status, medical illness severity or consumption of other drugs. Elderly patients on SSRIs or venlfaxine should have sodium levels checked before and after commencement of antidepressant treatment.     

Hyponatraemia and selective serotonin re-uptake inhibitors in elderly patients

Hyponatraemia (serum sodium arbitrarily defined as less than 135 mmol/L) is an increasingly recognised adverse effect of selective serotonin re-uptake inhibitors (SSRIs). Its precise prevalence and incidence in the elderly are hard to determine because of confounding factors including other prescribed medications and medical conditions. Although hyponatraemia has been reported with all SSRIs and venlafaxine, most studies are small, retrospective, limited by confounding variables or are individual case reports. The risk of developing hyponatraemia while on an SSRI seems to increase with age, female, sex, previous history of hyponatraemia and the concomitant use of other medications known to include hyponatraemia. The sodium concentrations of most patients with SSRI associated hyponatraemia return to normal within days to weeks of SSRI withdrawal. A few cases of SSRI rechallenge indicate that hyponatraemia may sometimes be a transient effect with tolerance developing over time. There is an urgent need for controlled, rigorous studies to confirm the extent of the association between SSRIs and hyponatraemia. Older drugs such as tricyclic antidepressants also need systematic study. It remains quite unclear whether any specific SSRI or venlafaxine has a stronger association with hyponatraemia than any other antidepressant drug.     

Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety

Data will be reviewed using the acoustic startle reflex in rats and humans based on our attempts to operationally define fear vs anxiety. Although the symptoms of fear and anxiety are very similar, they also differ. Fear is a generally adaptive state of apprehension that begins rapidly and dissipates quickly once the threat is removed (phasic fear). Anxiety is elicited by less specific and less predictable threats, or by those that are physically or psychologically more distant. Thus, anxiety is a more long-lasting state of apprehension (sustained fear). Rodent studies suggest that phasic fear is mediated by the amygdala, which sends outputs to the hypothalamus and brainstem to produce symptoms of fear. Sustained fear is also mediated by the amygdala, which releases corticotropin-releasing factor, a stress hormone that acts on receptors in the bed nucleus of the stria terminalis (BNST), a part of the so-called ‘extended amygdala.'' The amygdala and BNST send outputs to the same hypothalamic and brainstem targets to produce phasic and sustained fear, respectively. In rats, sustained fear is more sensitive to anxiolytic drugs. In humans, symptoms of clinical anxiety are better detected in sustained rather than phasic fear paradigms.     

The response of neurons in the bed nucleus of the stria terminalis to serotonin: Implications for anxiety

Substantial evidence has suggested that the activity of the bed nucleus of the stria terminalis (BNST) mediates many forms of anxiety-like behavior in human and non-human animals. These data have led many investigators to suggest that abnormal processing within this nucleus may underlie anxiety disorders in humans, and effective anxiety treatments may restore normal BNST functioning. Currently some of the most effective treatments for anxiety disorders are drugs that modulate serotonin (5-HT) systems, and several decades of research have suggested that the activation of 5-HT can modulate anxiety-like behavior. Despite these facts, relatively few studies have examined how activity within the BNST is modulated by 5-HT. Here we review our own investigations using in vitro whole-cell patch-clamp electrophysiological methods on brain sections containing the BNST to determine the response of BNST neurons to exogenous 5-HT application. Our data suggest that the response of BNST neurons to 5-HT is complex, displaying both inhibitory and excitatory components, which are mediated by 5-HT_1A, 5-HT_2A, 5-HT_2C and 5-HT₇ receptors. Moreover, we have shown that the selective activation of the inhibitory response to 5-HT reduces anxiety-like behavior, and we describe data suggesting that the activation of the excitatory response to 5-HT may be anxiogenic. We propose that in the normal state, the function of 5-HT is to dampen activity within the BNST (and consequent anxiety-like behavior) during exposure to threatening stimuli; however, we suggest that changes in the balance of the function of BNST 5-HT receptor subtypes could alter the response of BNST neurons to favor excitation and produce a pathological state of increased anxiety.     

Moclobemide in the treatment of hot flashes in postmenopausal women

This randomized, prospective, double-blind study evaluated the efficacy and tolerability of moclobemide, a reversible, selective inhibitor of monoamine oxidase-A, in reducing the frequency and severity of hot flashes. Thirty post-menopausal women were enrolled, and 28 were allocated to 5 weeks of treatment with moclobemide 150 mg (group 1, n = 10), moclobemide 300 mg (group 2, n = 11), or placebo (group 3, n = 9). Data on hot flashes were recorded in a daily diary. Mean reductions in the hot flash severity score were 24.4% in the placebo group, 69.8% in group 1, and 35.0% in group 2. This large difference suggests that the beneficial effects were not due to a placebo effect. Moclobemide may be a new nonhormonal option for reducing the incidence, severity, and duration of hot flashes in postmenopausal women who do not wish to take estrogen or have contraindications to its use.     

米氮平与SSRIs治疗难治性抑郁症对照研究

目的探讨米氮平与SSRIs治疗难治性抑郁症的临床疗效及安全性。方法将80例难治性抑郁症患者随机分为两组各40例,研究组口服米氮平治疗,对照组口服SSRTs药物治疗,观察12mo。于治疗前及治疗1mo、3mo、6mo、12mo末采用汉密顿抑郁量表和副反应量表评定临床疗效和不良反应,生存质量量表评定患者的生存质量。结果治疗12mo末,研究组有效率90.0%,对照组为72.5%,研究组显著高于对照组（χ^2=4.02,P〈0.05）。汉密顿抑郁量表评分,两组治疗1mo末起均较治疗前有显著性下降,同期研究组总分及各因子分均较对照组下降显著（P〈0.05或0.01）。生存质量量表评分,两组治疗1mo末起各因子分均较治疗前有显著提高,同期研究组各因子分均较对照组提高显著（P〈0.05或0.01）。两组不良反应均轻微,但研究组口干、多汗、便秘不良反应发生率显著低于对照组（P〈0.01）。结论米氮平对难治性抑郁症疗效肯定、能显著改善患者的生存质量、安全性更高、依从性更好。     

文拉法辛缓释胶囊治疗抑郁和焦虑障碍共病60例

目的 研究文拉法辛缓释胶囊治疗抑郁、焦虑障碍共病的疗效及安全性.方法 将120例抑郁、焦虑障碍共病患者随机均分为文拉法辛缓释胶囊组(研究组)和选择性5-羟色胺再摄取抑制剂组(对照组),进行对照研究,疗程12周,采用汉密顿焦虑量表、汉密顿抑郁量表、药物副作用量表评定临床疗效和不良反应.结果 研究组抗焦虑、抗抑郁作用均较对照组起效快(P＜O.05或P＜O.01),抗焦虑疗效优于对照组(P＜0.05);治疗12周末两组抗抑郁疗效相当.结论 文拉法辛缓释胶囊治疗抑郁、焦虑障碍共病起效快、疗效显著、安全性高、依从性好.