Selective serotonin reuptake inhibitors venlafaxine

Antidepressants Trazodone, mirtazapine, paroxetine, other selective serotonin reuptake inhibitors venlafaxine... 

Indeed, 5-HT is also a substrate for the 5-HT transporter, itself an important player in the treatment of depression, and more recently for the whole range of anxiety disorders spectrum (GAD, OCD, social and other phobias, panic and post-traumatic stress disorders). It is the target for SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, paroxetine, fluvoxamine, and citalopram or the more recent dual reuptake inhibitors (for 5-HT and noradrenaline, also known as SNRIs) such as venlafaxine. Currently, there are efforts to develop triple uptake inhibitors (5-HT, NE, and DA). Further combinations are possible, e.g. SB-649915, a combined 5-HTia, 5-HT1b, 5-HT1d inhibitor/selective serotonin reuptake inhibitor (SSRI), is investigated for the treatment of major depressive disorder. 

A number of non-hormonal therapies have been studied for symptomatic management of vasomotor symptoms, including antidepressants [e.g., selective serotonin reuptake inhibitors (SSRIs) and venlafaxine], herbal products (e.g., soy, black cohosh, and dong quai), and a group of miscellaneous agents (e.g., gabapentin, clonidine, and megestrol). The choice of therapy depends on the patient s concomitant disease states, such as depression and hypertension, and the risk for potential adverse effects. 

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. 

Selective serotonin reuptake inhibitors are considered to be less effective than TCAs for migraine prophylaxis and should not be considered first- or second-line therapy. However, they may be beneficial when depression is a significant contributor to headache. Preliminary data suggest a possible benefit with venlafaxine. 

Venlafaxine extended release, duloxetine, paroxetine, and escitalopram are FDA approved for treatment of GAD. Sertraline is also effective. Acute response and remission rates are approximately 65% and 30%, respectively. Imipramine may be used when patients fail to respond to selective serotonin reuptake inhibitors (SSRIs). In one trial, diazepam, trazodone, and imipramine had greater anxiolytic activity than placebo. 

The traditional scheme is complicated by the fact that some antidepressants exhibit characteristics of more than one class. For example, clomipramine, a tricyclic antidepressant (TCA) with side effects and toxicity similar to other TCAs, works more like the selective serotonin reuptake inhibitors (SSRls). Similarly, venlafaxine and duloxetine, which are usually grouped with the atypical antidepressants, have a side effect and safety profile comparable to the SSRls. Although a classihcation system based on mechanism of action offers some advantage (see Table 3.7), even this scheme is limited by the fact that antidepressants that work in the same way may have widely divergent side effect and safety profiles. In the following discussion, the traditional classification system is adopted. Although fraught with problems and inconsistencies. 

Drugs that may affect antihistamines include aluminum/magnesium-containing acids, cimetidine, erythromycin, ketoconazole, MAO inhibitors, and rifamycins (eg, rifampin). Drugs that may be affected by antihistamines include alcohol and CNS depressants, beta-blockers, MAO inhibitors, metyrapone, nefazodone, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine. 

Is Effexor more effective for depression than an SSRI Med Lett Drugs Ther 2004 46 15-16. Kirby D, Harrigan S, Ames D. Hyponatraemia in elderly psych iatric patients treated with selective serotonin reuptake inhibitors and venlafaxine a retrospective controlled study in an inpatient unit. Int 1 Geriatr Psychiatry 2002,17 231-237. 

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. 

FIGURE 43.1 Pharmacologic treatment algorithm for full syndrome pediatric PTSD. Based on a snythesis of consensus data and clinical reports in the adult and child literature. The author hers no responsibility for the use of this guideline by third parties. SSRI, selective serotonin reuptake inhibitor NEE, nefaza-done SIB, self injurious behavior VLF, venlafaxine VPA, valproic acid. 

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. 

Thase ME, Entsuah AR, Rudolph RL Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 178 234-241,2001... 

Another approach to correct neurotransmission is to inhibit the reuptake of the neurotransmitters into their presvnaptic endings. If the presynaptic reuptake mechanism of a neurotransmitter is blocked then more of the neurotransmitter will stay in the synaptic cleft and be functionally available. Many antidepressant drugs, called reuptake inhibitors , are thought to act via this mechanism. If selective for serotonin they are called selective serotonin reuptake inhibitors (SSRIs, Chapter 1), but if selective for both serotonin and noradrenaline they are called serotonin noradrenaline reuptake inhibitors (SNRIs). Most older antidepressants, such as the tricyclic compounds amitriptyline, imipramine and clomipramine, have little specificity for any of the neurotransmitters fluoxetine, paroxetine, citalopram and a few others are specific for serotonin venlafaxine is a representative of the SNRIs. A more recent mixed-uptake inhibitor is mirtazepine, and some similar compounds are about to be launched. 

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),... 

In addition to buspirone and the non-barbituate, non-BZP hypnotics, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and other new antidepressants all represent attempts to achieve anxiolytic and hypnotic effects seen with the BZDs, while avoiding their unwanted properties. 

Whyte IM, Dawson AH, Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM. 2003 96 369-374. 

Newer antidepressants (eg, fluoxetine, paroxetine, citalopram, venlafaxine) are mostly selective serotonin reuptake inhibitors and are generally safer than the tricyclic antidepressants and monoamine oxidase inhibitors, although they can can cause seizures. Bupropion (not an SSRI) has caused seizures even in therapeutic doses. Some antidepressants have been associated with QT prolongation and torsade de pointes arrhythmia. The SSRIs may interact with each other or especially with monoamine oxidase inhibitors to cause the serotonin syndrome, characterized by agitation, muscle hyperactivity, and hyperthermia. 

Altamura AC, Pioh R, Vitto M, Mannu P (1999) Venlafaxine in social phobia a study in selective serotonin reuptake inhibitor non-responders. Int Clin Psychopharmacol 14 239-245... 

These selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and, most recently, escitalopram (Lexapro see the appendix). These drugs block the removal of the neurotransmitter serotonin from the synaptic cleft. A number of other antidepressants are potent nonselective serotonin reuptake inhibitors (NSRIs). These include the atypical venlafaxine (Effexor) and the tricyclic clomipramine (Anafra-nil). Nefazodone (Serzone) has been withdrawn from the market due to liver damage. 

Fluoxetine (Prozac /Lilly), paroxetine (Paxil /GlaxoSmithKilne), and sertraline (Zoloft /Pfizer) are selective serotonin reuptake inhibitors (SSRIs) and are useful in the treatment of depression. These agents potentiate the pharmacological actions of the neurotransmitter serotonin by preventing its reuptake at presynaptic neuronal membranes. In addition to its SSRI properties, venlafaxine (EfFexor /Wyeth-Ayerst) also appears to be a potent inhibitor of neuronal norepinephrine reuptake and a weak inhibitor of dopamine reuptake thereby enhancing the actions of these neurotransmitters as well. Venlafaxine is indicated for use in anxiety and depression. 

Psychodynamic supportive psychotherapy (n = 107) has been compared with psychotherapy plus medication (n = 101) in patients with major depressive disorder (93). The medications included venlafaxine, selective serotonin reuptake inhibitors, nortriptyline, and nortriptyline plus lithium. Lithium was used as an augmentation strategy in the patients who took lithium and nortriptyline (number not given). There were no differences in outcomes between the two treatment groups. No adverse effects specific to lithium were reported. 

Several studies have examined the interaction between selective serotonin reuptake inhibitors (SSRIs) and P-gp and have shown that not all members of this class of drugs are P-gp substrates. Concentrations of paroxetine and venlafaxine/ but not fluoxetine/ were significantly increased in the brains of mdrla/b (—j—) knockout mice compared to concentrations in the wild-type mice.(100) In cell culture studies/ sertraline/ its metabolite desmethylsertraline/ and paroxetine were shown to be potent inhibitors of P-gp however/ citalopram and venlafaxine were only weak inhibitors (101/ 102). 

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