Selective serotonin reuptake inhibitors efficacy

Seretti A, Kato M, De Ronchi D, et al. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients. Mol Psychiatry 2007 12 247-57. 

Anderson IM, Tomenson BM (1994). The efficacy of selective serotonin reuptake inhibitors in depression a meta-analysis of studies against tricyclic antidepressants. / Psychopharmacol 8, 238 9. 

Selective serotonin reuptake inhibitors metaanalysis of efficacy and acceptability. Br Med J 306,683-7. 

Selective serotonin reuptake inhibitors (SSRIs) are considered the drugs of choice based on their tolerability and efficacy for social anxiety disorder as well as comorbid disorders. 

In many clinical trials a positive control of a clinically established drug is often used for comparison purposes for example, a novel selective serotonin reuptake inhibitor (SSRI), may be compared with a more established tricyclic antidepressant, such as imipramine. The aim is to see whether the new SSRI is more efficacious or has fewer adverse side effects than the more established tricyclic (Chapter 12). In many such comparisons the new and older treatments are equally efficacious at relieving depression, but the newer drugs display fewer side effects this means that they are better tolerated by patients, so that they are more willing to continue taking the tablets. The high rates of compliance also mean that, in overall terms, newer drugs with fewer side effects tend to be more efficacious. 

Alternatives to estrogen for hot flushes are shown in Table 31-6. Progesterone alone may be an option in women with a history of breast cancer or venous thrombosis, but side effects limit their use. For women with contraindications to hormone therapy, selective serotonin reuptake inhibitors and venlafaxine are considered by some to be first-line therapy, but efficacy of venlafaxine beyond 12 weeks has not been shown. 

Pigott TA, Seay SM. (1999). A review of the efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder. J Clin Psychiatry. 60(2) 101-6. 

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

In trials of hospitalized patients tricyclic antidepressants have generally been more efficacious than selective serotonin reuptake inhibitors (SSRIs). Otherwise there are no overall differences between the drugs in terms of tolerability or efficacy in primary care settings. After reviewing 15 trials it was concluded that drags are effective in the treatment of dysthymia with no differences between and within class of drugs. Tricyclic antidepressants are more likely to cause adverse events and dropouts. As dysthymia is a chronic condition, there remains little information on quality of life and medium or longterm outcome. 

The growth during the 1990s in the use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), for the treatment of anxiety disorders represented a major advance in the pharmacotherapy of anxiety. The efficacy of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) had been established alongside their antidepressantw actions several decades... 

Smith D, Dempster C, Glanville I, et al. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants a meta-analysis. Br 1 Psych iatry 2002,180 396-404. 

The efficacy of beta-blockers in the symptomatic relief of anxiety in adults has been established in over a dozen controlled trials (Neppe, 1989). In a number of countries, beta-blockers have been licensed for the treatment of anxiety disorders. Somatic manifestations of anxiety such as palpitations, diaphoresis, and tremor, rather than core psychological symptoms, were particularly responsive to beta-blocker treatment. In comparative trials that included patients with severe anxiety and panic attacks, the antianxiety effect of beta-blockers was, however, somewhat less powerful than that of benzodiazepines (Lader, 1988), with the exception of a small trial that compared alprazolam to propranolol (Ravaris et ah, 1991). Head-to-head comparisons of beta-blockers and selective serotonin reuptake inhibitors (SSRIs) are lacking. Performance and stress-related anxiety that may affect public performers, such as musicians or people taking an examination or giving a speech, seems to be particularly suited for beta-blocker treatment (Lader, 1988). Beta-blockers may be given on an as-required basis 1-2 hours before the stressful situation. 

In contrast, a less extensive but still convincing database has identified important clinical differences in efficacy for antidepressants used to treat patients with atypical or comorbid depression. Individuals with atypical depression (distinct quality of mood, hyperphagia, hypersomnia, psychomotor retardation, rejection sensitivity, and such unusual atypical features as chocolate craving] have superior responses to monoamine oxidase inhibitors (MAOIs], selective serotonin reuptake inhibitors (SSRIs), and perhaps venlafaxine, and most do not respond well to tricyclic antidepressants (TCAs] (Davidson et al. 1982 Liebowitz et al. 1988 Quitkin et al. 1988, 1991). Despite these data, TCAs unfortunately have been the first choice for most atypical patients until SSRIs were introduced. 

Roose SP, Glassman AH, Walsh BT, et al Tricyclic nonresponders phenomenology and treatment. Am J Psychiatry 143 345-348, 1986 Roose SP, Glassman AH, Attia E, et al Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. Am J Psychiatry 151 1735-1739, 1994... 

Song F, Freemantle N, Sheldon TA Selective serotonin reuptake inhibitors meta-analysis of efficacy and acceptabihty. BMJ 306(6879) 683-687, 1993 Song L, Jope R Chronic lithium treatment impairs phosphatidylinositol hydrolysis in membranes from rat brain regions. J Neurochem 58 2200-2206, 1992 Souza EG, Mander AJ, Goodwin GM The efficacy of lithium in prophylaxis of unipolar depression evidenced from its discontinuation. Br J Psychiatry 157 718-722, 1990... 

Perry PJ Pharmacotherapy for major depression with melancholic features relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants. J Affect Disord 39 1—6, 1996... 

It is thus understandable why some earlier authors previously doubted the efficacy of antidepressants in general (Weiner et al.. 1980) or the advantages of newer antidepressants compared with classical products (Song et al., 1993). However, the great majority of doctors and scientific authors consider that the efficacy of first-generation antidepressants (imipramine, amitriptyline, nortriptyline) has been proved beyond any reasonable doubt, and that efficacy also has been demonstrated for newer products such as trazodone, the selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake... 

Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

Despite the diagnostic challenges that remain in trying to understand the nature of MDD in children and adolescents, advances in its treatment has progressed considerably since the last edition of this textbook. Over this interval, selective serotonin reuptake inhibitors (SSRIs) have superseded TCAs as the treatment of first choice based both on efficacy and safety considerations. As in adults, specific psychotherapies (cognitive therapy, cognitive-behavioral therapy, and interpersonal therapy) may be as effective as antidepressant medication, at least in mild to moderate depression in children and adolescents ( 111, 112). Also, evidence indicates that depression in children and adolescents may be more influenced than is depression in adults by psychosocial variables such as peers and family, as well as other environmental factors (113). 

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