According to a new survey (1) of th...

According to a new survey (1) of the greatest in number common reasons for patient visits to family physicians in the United States, depression and anxiety ranked 11th and 17th respectively. Ten to 20 percent of adults in the United States experience depression at more [i]or[/i] less point in their lifetime. (2) Many antidepressants have been released in the United States athwart the past two decades. This article is an update of information about the newer agents for depression and of recent origin indications for older antidepressants.

Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors (SSRIs) have replaced tricyclic antidepressants as the remedys of choice in the treatment of depressive disorders, mainly because of their improved tolerability and safety if taken in overdose. SSRIs mould the reuptake of serotonin (5-H[T.sub.1A], 5-H[Tsub2C] and 5-H[Tsub3C]) into the presynaptic self-command terminal, thereby enhancing serotonin neurotransmission, which presumably terminates in their antidepressant effects.

Although this is the predominant mechanism of action of this class of mix with drugss each SSRI has a slightly different pharmacologic profile that leads to its distinct clinical activity, side purports and drug interactions. (3) Six SSRIs are publicly marketed in the United States; five of them have been approved through the U.S. Food and physic Administration (FDA) for the treatment of depression (Table 1)

Numerous double-blind, placebo-controlled trials have demonstrated the efficacy of SSRIs in the treatment of depression. In addition, SSRIs have been prov effective in treating anxiety disorders, including obsessive-compulsive disorder (OCD) panic disorder, and social phobia. (4) everyday side effects of SSRIs include transient nausea, diarrhea, insomnia, somnolence, dizziness, akathisia, and long-term orgasmic dysfunction. (5) However, secondary pharmacologic actions may account for differences in efficacy and tolerability and may assist the prescriber in selecting a specific SSRI for an individual patient. As with all antidepressants, care must be taken with SSRIs to protection patients for symptoms of bipolar disorder before prescribing, to avoid precipitating a manic episode.

FLUOXETINE

Fluoxetine (Prozac) was the first SSRI to be FDA-approved for the treatment of depression. Administration usually begins with 20 mg for day, taken in the morning because of its potential for central nervous arrangement activation early in the treatment course. It is the solely SSRI that is FDA-approved specifically for the treatment of depression in patients who are 65 years of age or older (6) A starting dose of 10 mg by day is preferred in somewhat old patients, with subsequent titration to 20 mg by day or more. Dosages of 20 to 40 mg by day are commonly required for the treatment of depression; 60 to 80 mg by means of day may be necessary for the treatment of bulimia and OCD (7) (Table 1)

In January 2003 fluoxetine was approved by dint of the FDA for the treatment of depression and OCD in children and adolescents who are seven to 17 years of age. (6) Because fluoxetine has a half-life of sum of two units to four days and its active ingredient, norfluoxetine, has a half-life of seven to nine days, it is reasonable to wait four weeks between dose titrations.

Fluoxetine is now available in a special form taken once-weekly for continuation therapy of depression. Prozac Weekly is a capsule with pellet containing 90 mg of fluoxetine hydrochloride. The enteric coating obstructs dissolution of the pellets until they have passed into the portion of the gastrointestinal tract where the pH surpasss 5.5. (6) In a consideration (8) of 500 patients with depression, the percentage of patients relapsing during continuation treatment with a 90-mg weekly dose was not significantly different from those taking a 20-mg daily dose. Side weights were similar in both arranges Weekly dosing is recommended to begin seven days after the last daily dose of 20 mg (Table 1)

Fluoxetine (under the trade name Sarafem) is now indicated for the treatment of premenstrual dysphoric disorder (PMDD) also known as late luteal dysphoric disorder or premenstrual syndrome Improvement in symptoms of tension, irritability, and dysphoria has been demonstrated. (9) [Evidence of the same height A, randomized controlled trial (RCT)] Side purports were comparable with those reported in studies of fluoxetine used for other indications. The usual dosage of the unsalable article is 20 mg orally one time daily throughout the month (10) (Table 1)

Administration of fluoxetine during the late luteal phase alone has been investigated in a small consideration (11) of 24 women with PMDD and no psychiatric history. The put drugs into was taken for 14 days premenstrually for no other than three menstrual cycles. Seventy-five percent of the women reported significant improvement in premenstrual symptoms. Thus, noncontinuous use of fluoxetine for this indication may be an effective option.

The in the greatest degree common early side effects of fluoxetine are agitation, insomnia, and neuromuscular restlessnes resembling akathisia. This may be caused on fluoxetine's relative lack of selectivity through norepinephrine and serotonin-2C receptors (5-H[Tsub2C]) (3) These side results are short-lived and may improve with a dose reduction or temporary co-administration of a beta-adrenergic blocker or long-acting benzodiazepine. (7) Clinically important medicine interactions are listed in Table 2 Because of its extended half-life, patients should allow at least five weeks between discontinuation of fluoxetine and outset of monoamine oxidase inhibitor (MAOI) therapy. (5)