Selective Serotonin Receptor Inhibitors Research Articles

Current alternative and complementary therapies used in menopause

Objective. To determine the efficacy and safety of common complementary and alternative medicine (CAM) therapies used to relieve the menopausal symptoms.Design. Comprehensive literature search was conducted through the databases Medline, EMBASE, Cochrane, AMED (Allied and Complementary Medicine), NCCAM (The National Centre for Complementary and Alternative Medicine) to identify relevant monographs in English language.Results. Studies have shown that some therapies such as clonidine, selective serotonin receptor inhibitors (SSRIs) and gabapentin are effective in decreasing the degree and frequency of somatic symptoms in menopause, while phytooestrogens and black cohosh have shown mixed results. Use of Ginseng, evening primrose, Dong Quai or vitamin E appears not to be efficacious for the relieving hot flushes. Other effects of these therapies including possible improvements in mood are yet to be substantiated.Inclusion criteria. All available human complementary medicine studies on menopausal women with regard to the relief of menopausal symptoms.Exclusion criteria. Studies not meeting the inclusion criteria, published in languages other than English or animal studies.Conclusion. There is a general lacking of longer-term follow-up beyond the trial lengths of 6–12 weeks in the use of CAM, although women may be taking these medications for many years. Well-designed, randomised control trials are needed to elucidate the true effect of these therapies above the placebo effect.

Pharmacotherapy of Mood Disorders and Treatment Discontinuation

Depression is the most frequent and costly problem in primary care, where most of these patients are seen and treated. In many countries, the public regard antidepressant drugs as 'addictive', partly because of the withdrawal symptoms that can occur when they are discontinued. Indeed, discontinuation (withdrawal) symptoms can follow the stoppage of almost all classes of antidepressants, including selective serotonin receptor inhibitors (SSRIs). This is important because they are widely regarded as drugs of choice for both depression and the anxiety disorders. But is this true withdrawal or merely rebound? The antidepressant discontinuation syndrome is characterised by the time-locked emergence of new, clearly defined and quantifiable signs and symptoms that ensue on stopping or reducing the dose of an antidepressant. Thereby, it meets the criteria for a withdrawal syndrome. The symptoms are not usually severe or protracted. SSRIs vary in their propensity to be associated with a discontinuation syndrome: paroxetine appears to be the most likely. Patients should be warned of the possibility of developing such a reaction, but reassured that it is usually mild and self limiting. Tapering the dose, if practicable, is worthwhile. In severe cases, temporary reinstatement of the SSRI and slower tapering may be necessary. Escalation of antidepressant dosage, or 'street abuse', is rare with antidepressants. The use of antidepressants is generally beneficial, and efforts should be made to optimise our current use of these drugs as well as encouraging the development of newer, better and innovative compounds. To this end, physicians should educate themselves and the public about discontinuation and withdrawal, so that these clinical features can be put in a realistic context.

Remission from Depression

Worldwide, major depression is the leading cause of years lived with a disability, and the fourth cause of disability-adjusted life years. Depression is second only to hypertension as the most common chronic condition encountered in general medical practice. Unfortunately, despite the high prevalence of depression, under-recognition and under-treatment are common.Historically, clinicians have assessed the short-term effectiveness of antidepressants by response rates, often defined as a 50% reduction in depressive symptoms. However, this usually does not reflect true clinical remission, and residual symptoms are common. Persistence of residual symptoms appears to be a common link to relapse, chronic disability and suicide. The burden of not treating depression effectively to remission is significant, as the disease is an important contributor to the disability levels of the general population. Disability, in turn, has a profound impact on lost productivity and medical expenses. In 2000, depression cost the US more than US 83 billion dollars annually in lost productivity, medical expenses and premature death.Venlafaxine, a dual-acting serotonin norepinephrine (noradrenaline) reuptake inhibitor, may improve a patient's response to treatment and their chances of achieving complete remission compared with conventional antidepressant therapies, with the evidence for this being the strongest for comparisons with the selective serotonin receptor inhibitors (SSRIs). To date, there are only a small number of economic studies of venlafaxine, and most are cost or resource utilisation analyses with significant limitations. Nevertheless, two cost-effectiveness analyses of venlafaxine are available. They found venlafaxine had a lower average cost per patient achieving remission or per symptom-free day compared with SSRIs; one reported an incremental cost-effectiveness ratio for venlafaxine of US 586 dollars (year 2002 values) per additional patient achieving remission over 8 weeks, and the other found venlafaxine to be a dominant treatment choice over SSRIs over 6 months (year 2001 values). Although requiring further confirmation, these initial data suggest that venlafaxine is a cost-effective strategy for the treatment of depression. The availability of an effective armamentarium of antidepressant strategies, including venlafaxine, to achieve and sustain remission offers both clinical and economic value to all those touched by the burden of depression.

Effects of the Committee on Safety of Medicines Advice on Antidepressant Prescribing to Children and Adolescents in the UK

Psychotropic medication prescribing for children and adolescents rose significantly between 2000 and 2002, including antidepressant prescribing. In 2003, the Committee on Safety of Medicines (CSM) advised against using venlafaxine or any selective serotonin receptor inhibitor (SSRI), with the exception of fluoxetine, for childhood and adolescent depression. The aim of this study was to compare the prevalence and incidence of children and adolescents who were prescribed antidepressants in UK primary care, before and after the CSM advice on antidepressant prescribing. We also compared paediatric antidepressant prescribing trends from Mediplus data with national antidepressant prescribing trends in England from the Prescription Pricing Authority (PPA). The Disease Analyzer-Mediplus database contains anonymised primary care records for about 3 million patients. Eligible patients were aged <or=18 years and received >or=1 antidepressant prescription between 2000 and 2004. Antidepressants were grouped according to the CSM advice and the British National Formulary. Prevalence and incidence were calculated. The prevalences of 2000, 2002 and 2004 were compared using a Chi-squared test. PPA data on antidepressant prescribing rates were compared with paediatric antidepressant prescribing rates from Mediplus. 5,718 children and adolescents received a total of 25,542 prescriptions between 2000 and 2004. The median number of prescriptions per patient was two (interquartile range 1-5). Common indications included depression and anxiety. Antidepressant prevalence increased from 2000 to 2002 (from 5.4 to 6.6 patients per 1,000 people), with a rise in the number of patients prescribed venlafaxine and SSRIs. However, between 2002 and 2004 there was a decrease in antidepressant prevalence (from 6.6 to 5.7 per 1,000). The prevalence of CSM-contraindicated antidepressants (citalopram, escitalopram, fluvoxamine, paroxetine, sertraline and venlafaxine) declined by a third (from 3.1 to 2.0 per 1,000), but there was no change in fluoxetine prevalence (from 2.1 to 2.3 per 1,000). The number of patients prescribed tricyclic antidepressants dropped marginally (from 2.0 to 1.7 per 1,000). Incidences followed the same trends as the prevalences, but there was a 48% reduction in the incidence of CSM-contraindicated antidepressants between 2002 and 2004. National antidepressant prescribing trends increased; paediatric prescribing trends were similar to national trends between 2000 and 2003; however, there was a 27% reduction in the paediatric prescribing rate of CSM-contraindicated antidepressants between 2002 and 2004. Since 2003, fewer children and adolescents have been prescribed antidepressants in primary care. However, fluoxetine and non-SSRI antidepressant prevalences have not risen, implying that they are not prescribed as alternative treatments. This study shows that the CSM advice has had a significant effect in reversing the rising prevalence of antidepressant prescribing to children and adolescents in primary care.

Antidepressants and Sleep

Most antidepressants change sleep; in particular, they alter the physiological patterns of sleep stages recorded overnight with EEG and other physiological measures. These effects are greatest and most consistent on rapid eye movement (REM) sleep, and tend to be in the opposite direction to the sleep abnormalities found in major depression, but are usually of greater degree. Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients. Antidepressants that increase serotonin function by blocking reuptake or by inhibiting metabolism have the greatest effect on REM sleep. The decrease in amount of REM sleep appears to be greatest early in treatment, and gradually diminishes during long-term treatment, except after monoamine oxidase inhibitors when REM sleep is often absent for many months. Sleep initiation and maintenance are also affected by antidepressants, but the effects are much less consistent between drugs. Some antidepressants such as clomipramine and the selective serotonin receptor inhibitors (SSRIs), particularly fluoxetine, are sleep-disturbing early in treatment and some others such as amitriptyline and the newer serotonin 5-HT2-receptor antagonists are sleep promoting. However, these effects are fairly short-lived and there are very few significant differences between drugs after a few weeks of treatment. In general, the objectively measured sleep of depressed patients improves during 3-4 weeks of effective antidepressant treatment with most agents, as does their subjective impression of their sleep. Sleep improvement earlier in treatment may be an important clinical goal in some patients, perhaps when insomnia is particularly distressing, or to ensure compliance. In these patients, the choice of a safely used and effective antidepressant which improves sleep in short term is indicated. Patients with other sleep disorders such as restless legs syndrome and REM sleep behaviour disorder should be identified before choosing a treatment, as some antidepressants worsen these conditions. Conversely, there is evidence that some antidepressants may be useful in the treatment of sleep disorders such as night terrors.

Identification of selected psychopharmaceuticals and their metabolites in hair by LC/ESI-CID/MS and LC/MS/MS

Hair samples of patients of psychiatry and hair samples of suicide cases were analysed by liquid-chromatography/ionspray-mass spectrometry (LC/MS) for antidepressants and neuroleptics. Electrospray ionisation (ESI) with in-source collision induced dissociation (ESI/CID) and tandem-mass spectrometry (MS/MS) were used for drug and metabolite identification. Mass spectra library searching was performed using an ESI/CID mass spectra library and a MS/MS spectra library. Furthermore, extracted ion chromatograms were used for the detection of N-desmethyl-metabolites, which were also identified by their fragment-ion spectra. Three examples using these methods are shown: The tricyclic antidepressant maprotiline, the selective serotonin receptor inhibitor (SSRI) citalopram and their desmethylmetabolites as well as the neuroleptic pipamperone were detected and identified in hair extracts. For extraction powdered hair was treated by ultrasonication in methanol and solid-phase extraction was used for sample clean-up prior to LC/MS or MS/MS analysis. These examples demonstrate the power of LC/MS and LC/MS/MS for the detection and identification of drugs in hair extracts using full-scan mode and ESI/CID with library searching or using highly selective LC/MS/MS-analysis with library searching or in multiple reaction monitoring mode.