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5-HT(2A) receptors down-regulate in young depressed subjects after treatment with paroxetine, but this down-regulation attenuates with age. This suggests that over 6 weeks paroxetine treatment increases 5-HT agonism on 5-HT(2A) receptors in the cortex of young patients with depression.

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Aim Men with Major Depressive Disorder (MDD) report high rates of sexual dysfunction, as do healthy males with low levels of testosterone. The objective of this study is to evaluate the effects of depression and low testosterone across various domains of sexual function. Methods Untreated depressed males (N=44) and age-matched healthy controls (N=50) had blood samples drawn to determine morning levels of total testosterone (TT) and bioavailable testosterone (BT). In addition, questionnaires regarding depressive symptoms as well as sexual function were administered. Main Outcome Measures Sexual function outcomes were measured using the Sex Effects (SexFX) Scale and depression severity was assessed with the Hamilton Rating Scale for Depression-17 item (HAMD-17). Results Using TT criteria, 27.9% of men were categorically defined as hypogonadal compared to 19.3% using BT criteria. Within both TT and BT hypogonadal groups, men with MDD had lower scores on all domains of sexual function compared to healthy controls with hypogonadism. Testosterone levels interacted with MDD status to affect orgasm and desire, although not arousal. Multiple linear regression analyses revealed that depression status was the main factor influencing sexual function. Hypogonadal status was not a predictor of sexual function in this sample, although age did play a minor role in the domain of arousal. Conclusion While testosterone levels appear to influence sexual function, specifically orgasm, the presence of MDD appears to be a stronger factor and has high predictive value for sexual outcomes.

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There is a recognized gap between knowledge derived from 'efficacy' data - based on usually brief randomized controlled trials and findings in natural practice 'effectiveness' studies. In considering the limitations of current antidepressants in clinical practice, we have selected three clinically important issues to examine in a natural practice data base that has been in existence for several years. These relate to: (1) Diagnostic heterogeneity and potential advances using functional brain imaging; (2) Variability of outcome measures during treatment and (3) Time to response and prediction of outcome. Copyright 2001 John Wiley & Sons, Ltd.

FIGURE 1. Mean T SE plasma A" 40 levels in dose groups among subjects completing the 6-month study: placebo (open circles), 1 g/d curcumin (small closed circles), and 4 g/d curcumin (large closed circles).Drug abuse history Yes = 13; No = 2; Not known = 3Prescribed medication Yes = 6 (including methadone in 1 case and diazepam in 2 cases); No = 6; Not known = 6Incident site Home/other specified residential place = 10; industrial site = 1; place of recreation = 1; river = 1; not known = 5Cause (s)/Mechanisms of death Ketamine and methadone toxicity Bronchopneumonia, hypoxic brain damage, cardiorespiratory arrest due to drug toxicity Combined GHB, amphetamine, and ketamine toxicity Drug abuse, bronchial asthma Drug overdose (morphine and ketamine) Ketamine and alcohol poisoning Opiate poisoning MDMA and ketamine overdose Drowning Complications of mixed drug intoxication, due to ingestion of alcohol, cannabis, ketamine, diazepam, MDMA, and heroin, followed by prolonged unconsciousness Stab wound to chest Pulmonary edema, cardiac arrhythmias, and drug intoxication Heroin poisoning Cerebral and pulmonary edema, mixed drug poisoning Cerebral and pulmonary edema, cocaine intoxication Respiratory depression, multiple drug poisoning Ketamine toxicity Ecstasy, ketamine, and GHB toxicity Drugs present at postmortem Alcohol, methadone, and ketamine Ecstasy, morphine/diamorphine, opiates, ketamine, and benzodiazepines Amphetamine, ketamine, ecstasy, cannabis, and GHB Alcohol, amphetamines, and ketamine Ethanol, ketamine, and morphine Alcohol, ketamine, and cannabis; Morphine, ketamine, cocaine, and codeine MDMA and ketamine Diazepam, ethanol, ketamine, temazepam, opiate-type, and substance Alcohol, cannabis, ketamine, diazepam, MDMA, and heroin Ketamine only (Â2) Ecstasy, ketamine, and ephedrine Heroin, ketamine, and temazepam Ethanol, cocaine and metabolites, ketamine, and morphine Cocaine and metabolites, diazepam and metabolites, ketamine, and cannabinoids MDMA, MDA, methylamphetamine, ketamine, amphetamine, cocaine and metabolites, and cannabis metabolites Ecstasy, ketamine, cocaine, and GHB Circumstances of death While drinking with others (Â2); while clubbing with others; injecting with partner; snorted while with others; collapsed during illegal rave; drowned; taken before killing himself with a knife; took with a range of other stimulants before engaging in gay sex with group of new acquaintances; overheated while wearing rubber body suit; took to excess trying to calm herself down; consumed range of drugs during a period of 2 days at various gay venues. Not known = 6 Verdict Accident/misadventure = 11; open = 2; suicide = 1; dependent abuse of drugs = 1; abuse of drugs = 1; nondependent abuse of drugs = 1; self-administered overdose of drugs = 1 Additional cases from GRO sources (1993-2006) England & Wales-ONS data: 3 deaths of accidental poisoning (1993-2002); 2 males and 1 female; ages within the range 20-49 years. Drugs mentioned: 2Â ketamine alone; 1 ketamine + coproxamol. Scotland (1994-2006): a 26-year-old woma...