SSRIs responses

Serretti, A., Cusin, C., Rossini, D. et al. (2004). Further evidence of a combined effect of SERTPR and TPH on SSRIs response in mood disorders. Am. J. Med. Genet. B Neuropsychiatr. Genet., 129B(1), 36-40. 

Based on existing findings, there are many important hypotheses in pediatric psychopharmacogenetics. Selective serotonin transporter inhibitors have been shown to have efficacy in double-blind studies in children and/ or adolescents in the treatment of autism, major depression, OCD, and anxiety disorders. Given the association of the serotonin transporter promoter variant with SSRI treatment response in adult depression (Smeraldi et ah, 1998), all of the SSRI-responsive phenotypes should be tested for promoter variant influence on response using family-based or population-based controlled association studies. The report of strong 5-HTTLPR allelic effects on SSRI-induced mania (Mundo et ah, 2000) is of special interest given frequent SSRI-induced activation in children. 

When medications are used, treatment is typically started with an SSRI. Responses may take weeks or months to occnr. For example, OCD tends to have a rather large latency period before a benefit is observed. Panic disorder and social phobia tend to respond sooner, although, like depression, the lag period is measured in weeks, not days. A notable exception is the group of benzodiazepines, which have an almost instantaneous antianxiety effect. However, their use is limited because of possible cognitive side effects and the potential for addiction in susceptible populations. 

The 1 allele occurs at a frequency of 20% to 26% in Asian populations and about 53% to 55% in Caucasians [83-86]. In Caucasians and Chinese, the 1/1 genotype has been associated with a significantly better and faster SSRI response, while the s/s allele is associated with poor response [83,84,87-97]. In two studies in Japanese and Korean patients, one found that neither the 1 nor s allele had an effect on treatment response the other observed only a slight improved response among s allele carriers [98,99]. The 1 allele has been associated with improved response to paroxetine, fluoxetine, sertraline, and tricyclic antidepressants in depressed patients, while the s allele has been associated with both poorer response and greater incidence... 

Stein MB, Seedat S, Gelernter J. Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder. Psy chopharmacol 2006 187 68-72. 

The TCAs, such as amitriptyline (Elavil) and dox-epin (Sinequan), inhibit reuptake of norepinephrine or serotonin at the presynaptic neuron. Drug classified as MAOIs inhibit the activity of monoamine oxidase a complex enzyme system that is responsible for breaking down amines. This results in an increase in endogenous epinephrine, norepinephrine and serotonin in the nervous system. An increase in these neurohormones results in stimulation of the CNS. The action of the SSRIs is linked to their inhibition of CNS neuronal uptake of serotonin (a CNS neurotransmitter). The increase in serotonin levels is thought to act as a stimulant to reverse depression. 

Each antidepressant has a response rate of approximately 60% to 80%, and no antidepressant medication or class has been reliably shown to be more efficacious than another 22 MAOIs may be the most effective therapy for atypical depression, but MAOI use continues to wane because of problematic adverse effects, dietary restrictions, and possibility of fatal drug interactions.22,28 There is some evidence that dual-action antidepressants, such as TCAs and SNRIs, may be more effective for inpatients with severe depression than are the single-action drugs such as SSRIs,22,28 but the more general assertion that multiple mechanisms of action confer efficacy advantages is quite controversial.33... 

The initial dose of SSRI is similar to that used in depression. Patients should be titrated as tolerated to response. Many patients will require maximum recommended daily doses. Patients with comorbid panic disorder should be started on lower doses (Table 37-4). When discontinuing SSRIs, the dose should be tapered slowly to avoid withdrawal symptoms, with the possible exception of fluoxetine. Relapse rates may be as high as 50%, and patients should be monitored closely for several weeks.58 Side effects of SSRIs in SAD patients are similar to those seen in depression and most commonly include nausea, sexual dysfunction, somnolence, and sweating. 

Venlafaxine extended release, in doses of 75 to 225 mg/day, improves social anxiety, performance, and avoidance behavior with a reduction in disability.61 Treatment with venlafaxine results in response rates similar to those seen with paroxetine.60 Venlafaxine may be effective in SSRI non-responders.62 As with SSRIs, doses should be tapered slowly when discontinuing therapy. Tolerability is similar to that observed in depression trials with venlafaxine extended release. Common side effects are anorexia, dry mouth, nausea, insomnia, and sexual dysfunction. 

SSRIs are theorized to reduce the frequency of hot flashes by increasing serotonin in the central nervous system and by decreasing LH. Of the SSRIs, citalopram, paroxetine, and sertraline all have been studied and have demonstrated a reduction in hot flashes while treating other symptomatic complaints such as depression and anxiety.33 Venlafaxine, which blocks the reuptake of serotonin and norepinephrine, has demonstrated a reduction in hot flashes primarily in the oncology population.34 Overall, these antidepressant medications offer a reasonable option for women who are unwilling or cannot take hormonal therapies, particularly those who suffer from depression or anxiety. These agents should be prescribed at the lowest effective dose to treat symptoms and may be titrated based on individual response. 

Switching non-responsive patients from an SSRI to an SNRI led 25 per cent of them to get better. Change from an SSRI to bupropion produced virtually the same remission rate (26 per cent). But what of the patients who were not switched to a different class of antidepressant, but instead were simply given another SSRI Twenty-seven per cent of these patients also got better - a remission rate that is virtually identical to that produced by changing to a different type of medication. In other words, the rate of improvement did not depend on the kind of drug to which the patient had been switched. Simply changing from one SSRI to another was as effective as changing to a completely... 

Andrea Cipriani et al., 2009. The calculations are simple and straightforward. Table 3 of The Lancet article reports response rates for head-to-head comparisons of different antidepressants, along with the number of subjects on which each response rate was based. I merely extracted the response rates in all of the head-to-head comparisons of an SSRI with an NDRI, multiplied each response rate by the number of subjects it was based on, summed the product and divided... 

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