Major depressive disorder SSRIs

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. 

Traditionally, SSRIs have been used in the treatment of depression. Yet we are discussing their use for treating anxiety. When two or more distinct mental disorders can be observed in the same person, the disorders are said to be comorbid. There is a high rate of comorbidity for depression and anxiety. Some 59.2% of people who have a major depressive disorder also have some form of an anxiety disorder. 

The overall efficacy among the SSRIs for major depressive disorder is remarkably similar, consistent with the hypothesis that they have the same mechanism of action (i.e., serotonin uptake inhibition). 

Indications that there may be antidepressant synergy from dual 5HT-NE actions that correspond with these theoretical molecular events comes from studies in which venlafaxine has produced increased remission rates in major depressive disorders as compared with SSRIs. Increased remission rates with the TCAs over the SSRIs have also been reported and support the concept of dual action being more efficacious than SSRI action alone for remission of depression in some patients. 

The therapeutic efficacy and onset of action of an SSRI in obsessive compulsive disorder is very similar to that of an SSRI in major depressive disorder. 

Committee on Safety of Medicines. Selective Serotonin Reuptake Inhibitors (SSRIs) overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data. http /medicines.mh-ra.gov.uk/ourwork/monitorsafequalmed/safetymessages/ ssrioverview 101203.htm, updated 8.10.2004. 

Well accepted for use in schizophrenia and bipolar disorder, including difficult cases Documented utility in treatment-refractory cases, especially at higher doses Documented efficacy as augmenting agent to SSRIs (especially fluoxetine) in nonpsychotic treatment-resistant major depressive disorder Documented efficacy in bipolar depression, especially in combination with fluoxetine... 

Often a preferred treatment of anxious depression as well as major depressive disorder comorbid with anxiety disorders Withdrawal effects may be more likely than for some other SSRIs when discontinued (especially akathisia, restlessness, gastrointestinal symptoms, dizziness, tingling, dysesthesias, nausea, stomach cramps, restlessness)... 

There has been recent concern from unpublished data in industry-sponsored trials of SSRIs in child and adolescent depression suggesting that these drugs may lead to an increased rate of suicidal ideation. This prompted a review of their use by the UK Committee on Safety of Medicines (CSM) in 2003, which raled that for major depressive disorder (MDD) in children and adolescents under the age of 18 ... 

As a rule of thumb, all antidepressant drugs have comparable efficacy but different adverse effects profiles, although there are a few exceptions to this (e.g. selective serotonin reuptake inhibitors (SSRIs) are less efficacious in severe major depressive disorder). 

SSRIs), in the past 20 years has significantly affected the treatment of depression. The SSRIs have become first-line therapy in the treatment of major depressive disorder, and they also are used as adjunct treatment in other mood disorders. This new generation of antidepressants has more favorable side effect and pharmacokinetic profiles than the older generations of antidepressants, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). This has resulted in improved patient compliance and therapeutic outcomes for patients with major depressive disorder. 

Reboxetine is a nontricyclic SNRI in which the propylamine side chain of the TCAs is constrained into a morpholine ring (Fig. 21.8). It is a potent and selective ligand for the NET, with a mechanism of action is similar to that of desipramine. Reboxetine is used for the treatment of major depressive disorders. It is a chiral compound that is marketed as a racemic mixture of R,R- and S,S-reboxetine. The antidepressant activity for reboxetine appears to reside with the S,S-(+)-enantiomer, which has approximately twofold the inhibition potency of the R,R-enantiomer (42). It is well tolerated, with different adverse-event profiles, and it appears to be at least as effective as the SSRIs in the treatment of depressive illness. Currently, it is available only in Europe and is under U.S. FDA review. It preferentially inhibits the reuptake of NE (5-FIT NE ratio, 8). Reboxetine is not metabolized by the polymorphic isoforms, CYP2D6 or CYP2C19, and may offer a valuable alternative to the secondary amine TCAs in the treatment of major depression. Reboxetine is likely to become a promising alternative for patients who have failed treatment with or do not tolerate serotonergic antidepressants. Reboxetine has been shown to be effective and well tolerated in the treatment of panic... 

Monoamine oxidase inhibitors, such as SSRIs, have been shown to be effective in the treatment of depression, and they have become among the most widely used prescription drugs in the United States. Prozac is used not only to treat major depressive disorders but also bulimia nervosa, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder. Multiple serotonin receptor subtypes are involved. Specific serotonin receptor subtype agonists and antagonists have been radiolabeled with positron-emitting tracers to assess the state of the serotonergic system. 

The client with a major depressive disorder taking the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) calls the psychiatric clinic and reports feeling confused and restless and having an elevated temperature. Which action should the... 

The client diagnosed with a major depressive disorder asks the nurse, Why did my psychiatrist prescribe an SSRI medication rather than one of the other types of antidepressants Which statement by the nurse would be most appropriate ... 

Mischoulon D, Opitz G, Kelly K, Fava M, Rosenbaum JF. A preliminary open study of the tolerability and effectiveness of nefazodone in major depressive disorder comparing patients who recently discontinued an SSRI with those on no recent antidepressant treatment. Depress... 

Drug-drug interactions SSRIs Aripiprazole had no effects on the pharmacokinetics of escitalopram, fluoxetine, paroxetine, sertraline, or venlafaxine either in healthy subjects ( =63) or in patients with major depressive disorder ( =498) [69. Point estimates for mean plasma concentration ratios indicated no substantial effect of aripiprazole on any antidepressant escitalopram 0.97 (0.91-1.03), fluoxetine 1.18 (1.05-1.32), paroxetine 0.73 (0.60-0.89), sertraline 0.96 (0.89-1.04), or venlafaxine 0.97 (0.89-1.05). 

Vilazodone is both an SSRI and a partial serotonin 5-HTl A receptor agonist. In January 2011, vilazodone received FDA approval as an antidepressant suitable for use in adults. To date there have been relatively few reports concerning the adverse effect profile of vilazodone the available data mainly derive from two Phase 111 trials and an open label study. In a 1-year open-label study assessing the safety and tolerability of vilazodone in subjects with major depressive disorder, the most common adverse effects were diarrhoea (37.5%), nausea (31.6%) and headache (20.0%) however more than 90% of these adverse effects were rated as only mild or moderate http //en.wikipedia.org/wi ki/Vilazodonehttp //en.wikipedia.org/wiki/Vilazodone - cite note-intj-6 [90 -]. These adverse effects were somewhat higher than from the pooled Phase HI data, where the rates of these side effects were diarrhoea (28.4%), nausea (23.4%) and headache (13.3%) [91E,92E]. 

Placebo-controlled trial T3 has been used to enhance the effects of antidepressant drugs but results have been mixed (SEDA-32, 764 SEDA-33,882). Results of the largest prospective placebo-controlled trial to date indicate that T3 does not augment the effects of the SSRI, sertraline in the treatment of recent-onset major depressive disorder (MDD) [14 ]. 

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

Antidepressant drugs are used to manage depressive episodes such as major depression or depression accompanied by anxiety. These drugs may be used in conjunction with psychotherapy in severe depression. The SSRIs also are used to treat obsessive-compulsive disorders. The uses of individual antidepressants are given in the Summary Drug Table Antidepressants. Treatment is usually continued for 9 months after recovery from the first major depressive episode. If the patient, at a later date, experiences another major depressive episode, treatment is continued for 5 years, and with a third episode, treatment is continued indefinitely. 

The current SSRIs in the United States inclnde fluoxetine, fluvoxamine, sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro). All effectively treat major depression. In addition, one or more of the SSRIs has been shown effective in the treatment of dysthymic disorder, the depressive phase of bipolar disorder, premenstrual dysphoric disorder, panic disorder, social phobia, obsessive-compnlsive disorder, bnlimia nervosa, and binge-eating disorder. 

Fluvoxamine (Luvox). This is actually the oldest of the SSRIs. It is approved iu this couutry for the treatmeut of OCD but is also an effective treatment for major depression and many other anxiety disorders. It should be started at 50mg/day, and the effective dose range is from 100 to 300mg/day. Fluvoxamine is the only SSRI that must be takeu twice a day. The common side effects of fluvoxamine are comparable to other SSRIs. 

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