Posted by jb on March 13, 2001, at 14:42:10
Hope you find this as informatiive as I did. The basic conclusion, from what I can tell, is that all the SSRI's cause sexual dysfunction. The newer non-SSRI's, such as Remeron, Bupropion, and Serzone don't cause sexual dysfunction. Web site for the full artile is at the bottom.
John B (:)
The adverse effect slowest to be recognized is the SSRIs’ potential to produce sexual dysfunction in both genders. Current estimates are 20%–40% incidence, with reports as high as 75% when direct interviews are used. The dysfunctions reported include anorgasmia, decreased libido and male erectile problems. Strategies to deal with SSRI-induced sexual dysfunction include simply waiting or lowering the dose to decrease this effect, although it often persists. Another approach is to switch to an antidepressant not associated with sexual dysfunction, such as bupropion, nefazodone, or mirtazapine. Other options include allowing for a weekend “holiday,” in which the SSRI is taken on Thursday and restarted on Sunday. This will only work with the shorter half-life drugs, and the potential for withdrawal must be considered. The final option is to administer a second drug with the SSRI to counteract the SSRI’s sexual side effects. Probably the best studied agents in this situation have been bupropion and buspirone (Buspar). Given daily with the SSRI, these medications may also augment the antidepressant effect of the SSRI. The remaining agents are usually dosed 1–2 hours before sexual intercourse and include cyproheptadine (Periactin), yohimbine products, sildenafil (Viagra) and dopamine agonists such as methylphenidate (Ritalin), amantadine (Symmetrel) and bromocriptine (Parlodel).
Other New Generation Antidepressants
Trazodone (Desyrel): The primary use of trazodone in psychiatry today is as a safe, nonaddicting sleep medication. Trazodone is highly sedating, requiring slow dosage titration to achieve antidepressant doses of 200–600 mg/day administered in two to three divided doses. Slow titration is also necessary to avoid serious orthostatic hypotension. The patient is started at 50–100 mg/day at bedtime and the dose is slowly increased to the therapeutic range. Hypnotic doses range from 25–150 mg. Other adverse effects include headache, nausea, dizziness and, rarely, priapism. Trazodone is also used in elderly patients for agitation secondary to dementia and is given to treat activation side effects caused by SSRIs.Venlafaxine (Effexor): Venlafaxine is the first non-TCA antidepressant to block reuptake of both 5-HT and NE, as well as DA at high doses. As effective as SSRIs, it appears to show more rapid and possibly superior response, especially in severe depression. With a half-life of 4–10 hours for the combined parent drug and active metabolite, it required BID–TID dosing, prior to release of its once-daily Effexor XR dosage form in November 1997. The typical starting dose is 75 mg/day increased slowly (at least 4-day intervals) in increments of 75 mg/day up to a maximum of 375 mg/day.
Venlafaxine is an activating antidepressant, associated with anxiety, nervousness, and insomnia at twice the rate of placebo. As with SSRIs, long-term use may be associated with less anxiety. The most common side effect is nausea, which often necessitates very slow dosage titration. Other adverse effects include abnormal dreaming, abnormal ejaculation, anorexia, dizziness, dry mouth, sweating, tremor, and somnolence. Venlafaxine is also associated with an elevation in supine diastolic blood pressure in 3%–13% of patients, requiring ongoing blood pressure monitoring. This effect is dose-related, with most clinically significant elevations occurring at doses of 300 mg/day or greater.27 Although potentially problematic, BP elevation is not considered by most clinicians a contraindication to use in hypertensive patients. Venlafaxine has a low potential for drug interactions. It should not be given with MAOIs. Because venlafaxine is metabolized by cytochrome P4502D6 to its active metabolite, it is possible for inhibitors of this isozyme (such as cimetidine) to increase its serum levels.
Bupropion (Wellbutrin): Bupropion is an effective antidepressant having no direct effect on serotonin levels. It is considered one of the most activating antidepressants and can be particularly useful in cases of severe depression characterized by extreme fatigue, lethargy, and psychomotor retardation. Its ability to elevate dopamine levels is probably responsible for its positive effects in treating attention deficit hyperactivity disorder (ADHD), refractory depression, and in helping to reduce relapse rates in persons quitting cigarette smoking (Zyban). Typical depression starting doses range from 50–100 mg/day slowly titrated up to 200–600 mg/day. Before the introduction of Wellbutrin SR, daily doses were given q 8 h to maintain peak serum as low as possible to avoid seizures. The SR form, dosed q 12 h, has significantly lowered peak serum levels, as well as the relative seizure risk when doses are at 300 mg/day or lower.
Bupropion is contraindicated in patients with seizure disorders, eating disorders and in the concurrent use of MAOIs. Bupropion causes few cardiovascular effects, no anticholinergic effects, little sedation, and no more sexual dysfunction than placebo. Activating side effects such as agitation, insomnia, restlessness and anxiety are common. Other adverse effects include dry mouth, constipation, headache, nausea, excessive sweating, tremor, and weight loss. It has a very favorable drug interaction profile with the exception of MAOIs. Concurrent administration with methyldopa is associated with a higher incidence of adverse experiences.20
Nefazodone (Serzone): Nefazodone combines moderate reuptake inhibition of 5-HT and NE with potent blockade of the 5-HT2 receptor to produce a calming antidepressant that is particularly useful for agitated depression, mixed anxiety and depression and fibromyalgia. It is as effective as TCAs and SSRIs and has demonstrated efficacy in treating severe, major depression.29 It is initiated at doses of 100 mg twice daily and titrated to an effective range of 300–600 mg/day. Due to its short half-life, it requires twice-daily dosing, although some clinicians may administer most, if not all, of the total daily dose at bedtime to utilize its sedating qualities.
Somnolence, dry mouth, nausea, dizziness, and constipation are the most common adverse events.17 Others include headache, weakness, lightheadedness, blurred vision, confusion, and abnormal vision consisting of “vapor trails” in the visual field. It produces no more sexual dysfunction than placebo and less dizziness than its chemical cousin, trazodone. Nefazodone is a potent inhibitor of cytochrome P4503A4, capable of elevating serum levels of a number of medications (see TABLE 7). Of particular concern are the benzodiazepines, alprazolam and triazolam, which should have their doses reduced by 50% and 75%, respectively, if nefazodone is added to the regimen. Concurrent administration of astemizole and cisapride are considered relative contraindications, since high serum levels of these drugs can lead to cardiac problems and possible death. The concurrent administration of MAOIs is also contraindicated by the manufacturer, who advises a 7-day washout period for nefazodone before starting an MAOI, and a 14-day washout of the MAOI before starting nefazodone.
Mirtazapine (Remeron): Mirtazapine has the most complicated mechanism of action of any antidepressant, increasing 5-HT and NE while blocking 5-HT2 and 5-HT3 receptors. Its tolerability is limited by its potent histamine-1 blockade, associated with sedation and weight gain. A calming medication, it promotes sleep restoration and may be particularly effective in treating agitated depression, mixed anxiety and depression, and fibromyalgia. At least one report found mirtazapine superior to fluoxetine after 3 and 4 weeks of therapy.30 Its long half-life allows for once-daily dosing. The recommended starting dose is 15 mg/day with additional increases every 1–2 weeks to an effective range of 15–45 mg/day. In the premarketing trials conducted in the U.S., patients seldom exceeded 35 mg/day. In non-U.S. trials, patients were started at 15 or 20 mg/day and were titrated up to 60 mg/day. The non-U.S. trials reported substantially lower incidences of somnolence, dizziness, increased appetite and weight gain. These higher incidences at the lower doses may be due to unopposed histamine block counteracted by the increased release of NE at the higher doses.31
Somnolence, increased appetite, weight gain, and dizziness are the most common adverse reactions reported. Typically, these dissipate over time. Anticholinergic side effects were minor, with only dry mouth and constipation exceeding placebo rates. Cardiovascular side effects are minimal and sexual dysfunction is no greater than with placebo. Mirtazapine also lacks the activating and GI side effects seen with SSRIs, probably due to its 5-HT2 and 5-HT3 blocking effects. Because it is metabolized via multiple cytochrome P450 isozymes, but does not inhibit any of these isozymes to any appreciable degree, its drug interaction profile appears very positive. Alcohol and benzodiazepines produce additive sedative, psychomotor and cognitive effects when combined with mirtazapine. The manufacturer recommends that mirtazapine not be given in combination with MAOIs, or within 14 days of initiating or discontinuing MAOI therapy.
See this website for the full article:
http://www.uspharmacist.com/NewLook/CE/Depression/lesson.cfm
poster:jb
thread:56399
URL: http://www.dr-bob.org/babble/20010310/msgs/56399.html