J. Gitlin, MD article excerpt from Medscape - has anyone tried any of these?

[Guest guest]

Treatment of Sexual Side Effects: Antidotes

A variety of antidotes have been reported to treat

SSRI-induced sexual dysfunction effectively; however,

virtually all the data on these agents are derived

from open case reports and case series. Insofar as

sexual function improvement may be responsive to

placebo effects, it is impossible to estimate the true

efficacy of these antidotes.[27]

Most of these antidotes either have serotonin-blocking

properties (especially 5HT-2 antagonistic effects) or

augment catecholamine activity, especially that of

dopamine. The antiserotonergic antidotes are

cyproheptadine, buspirone, nefazodone, and mianserin.

Medications enhancing dopaminergic tone include

amantadine, bupropion, and stimulants, with yohimbine

showing noradrenergic effects. Among the reported

antidotes, the only 2 without antiserotonergic effects

or catecholaminergic activity are gingko biloba and

urecholine.

Cyproheptadine is an antihistamine with

antiserotonergic properties that has been reported for

over a decade to reverse antidepressant-induced sexual

dysfunction. Only case reports and case series attest

to its efficacy.[13,42-44] Effective doses range from

2mg to 16mg. In the most recent and largest case

series, 12 of 25 patients described improvement in

sexual function when treated with cyproheptadine (mean

dose, 8.6mg).[13] Anorgasmia is the sexual side effect

most often reported to be alleviated by

cyproheptadine. Cyproheptadine is effective when taken

either on an as-needed basis (typically, 1 to 2 hours

before intercourse) or on a regular basis.

However, cyproheptadine's utility is often limited by

its potential side effects. Excessive sedation and the

reversal of the therapeutic effect of the

antidepressant are major problems that limit its

usefulness. Effectively treated depression and bulimic

symptoms have been reported to reemerge soon after

cyproheptadine was started.[42,45-48] This reversal of

therapeutic effects is itself reversible upon

discontinuation.

Buspirone is a serotonin-IA partial agonist typically

prescribed to treat persistent anxiety. One case

series reported that buspirone reversed both decreased

sexual interest and orgasmic dysfunction caused by

SSRIs.[49] Most patients using buspirone to treat

sexual dysfunction take it daily. The dosage is the

same as that used for anxiety (15mg to 60mg daily).

The mechanism of action of buspirone in treating

sexual dysfunction may be reduction of serotonergic

tone via stimulation of presynaptic autoreceptors or

the alpha-2 antagonist effects of one of buspirone's

major metabolites, 1-pyrimidinylpiperazine.

Nefazodone and mianserin are antidepressants with

strong postsynaptic blocking properties. In one case

report, nefazodone 150mg taken 1 hour prior to sexual

activity completely reversed sertraline-induced

anorgasmia.[50] Mianserin, an antidepressant with

5HT-2 and alpha-2 adrenergic antagonist properties, is

available in many countries but not in the US. It has

been reported to reverse serotonin reuptake

inhibitor-induced sexual dysfunction in 9 of 15

patients.[51] Mirtazapine is similar in its biological

activity to mianserin and might also be effective in

reversing sexual side effects. No case reports or case

series have yet been published attesting to this,

although clinicians have described such an effect. The

putative capacity of mianserin and mirtazapine to

reverse sexual side effects can be attributed either

to their serotonergic activity or presynaptic alpha-2

activity.

Amantadine, a dopamine agonist, is used both as an

antiviral agent and as a treatment for Parkinson's

disease. It has been shown in a number of small case

series to reverse anorgasmia.[13,52-54] Reported

effective doses have ranged between 100mg to 400mg

taken either on a daily or as-needed basis. In the

most recent case series, 8 (42%) out of 19 patients

with SSRI-induced sexual dysfunction improved with

amantadine 200mg daily.[13] Given dopamine's

consistent effect as a neurotransmitter involved in

sexual arousal, a number of other dopamine agonists

have been explored as treatments for sexual side

effects.[2,55,56]

Bupropion is another commonly touted antidote for

SSRI-induced sexual dysfunction.[57,58] It is assumed

that the mechanism of action by which bupropion

reverses sexual side effects is its weak dopamine

agonism. The evidence for bupropion's efficacy is

scant, except for unpublished, anecdotal reports, one

case report,[57] and a case series[58] in which 31

(66%) of 47 patients showed improvement when bupropion

was added to the regimen along with the serotonergic

antidepressant. Most patients (18/31) with a

successful outcome responded to as-needed use of

bupropion 75mg to 150mg. Libido, arousal, and orgasmic

difficulties were all effectively reversed. Fifteen

percent of treated patients stopped taking bupropion

because of its stimulation side effects. It is unclear

whether bupropion doses need to be somewhat lower than

usual when added to fluoxetine or paroxetine, to

compensate for pharmacokinetic interactions resulting

in increased bupropion levels.[59]

Stimulants, such as methylphenidate, D-amphetamine,

and pemoline, are reported to reverse a variety of

sexual side effects caused by SSRIs or MAOIs.[60-62]

Low doses of 10mg-25mg of methylphenidate or

D-amphetamine have been effective. One should add

stimulants to an MAOI with extreme caution because of

the risk of a hypertensive episode. However, use of an

MAOI/stimulant combination has been shown to be safe

in a case series.[63] SSRI/stimulant combinations show

no similar risks.

Yohimbine is available with or without a prescription

(and with unclear purity) in health food stores. It is

an alkaloid from the bark of Corynanthe yohimbi

(family, Rubiaceae) and has been used for decades to

reverse erectile dysfunction.[64-66] Its efficacy in

treating sexual dysfunction may be associated with its

ability to block presynaptic alpha-2 adrenergic sites,

leading to enhanced adrenergic tone.[65] A variety of

sexual side effects have been reported to be

alleviated by yohimbine in doses ranging from 2.7mg to

16.2mg daily, prescribed either on a regular 5.4mg 3

times daily basis or on an as-needed basis with single

doses up to 16.2mg.[13,67-69] In the largest case

series, 17 (81%) of 21 patients showed improvement of

sexual side effects when treated with yohimbine (mean

dose, 16.2mg).[12]

Typical side effects associated with yohimbine include

anxiety, nausea, flushing, urinary urgency, and

sweating. Yohimbine has been the subject of the only

double-blind, placebo-controlled study to evaluate

treatment of sexual dysfunction occurring as a drug

side effect.[27] Unfortunately, the placebo effect was

marked, showing a minimal drug-placebo difference with

yohimbine given at a dose of 5.4mg 3 times daily.

Yohimbine is also available in lower potency without a

prescription. The purity, potency, and safety of these

preparations, however, are unknown.

Bethanechol is a cholinergic agonist that has

occasionally been useful in reversing sexual

dysfunction associated with TCAs and MAOIs.[70-73]

Typical doses are 10mg to 20mg as needed or 30mg to

100mg daily in a divided dose. Potential side effects

with bethanechol include diarrhea, cramps, and

diaphoresis. No reports have evaluated or suggested

the efficacy of bethanechol for treating SSRI-induced

sexual side effects.

Gingko biloba is an herbal extract reported to reverse

a variety of sexual dysfunctions associated with

antidepressants. Information about gingko's ability in

this regard is derived from the experience of 1

clinician presenting a large case series.[74] The

response rate was greater than 80%, with doses ranging

from 60mg twice daily to 120mg twice daily (mean daily

dose, 207mg). Reported side effects include

gastrointestinal upset, lightheadedness, and

stimulation effects. Because gingko may inhibit

platelet-activating factor, caution should be used in

considering its use by any patient with a bleeding

diathesis. The mechanism by which gingko might

alleviate sexual dysfunction is unknown.

Summary

Treating sexual dysfunction associated with

antidepressant medication is an important but

relatively unexplored issue in psychopharmacology. A

thoughtful diagnostic evaluation, including

examination of the possibility that some sexual

difficulties attributed to the antidepressant may have

another etiology, is mandatory. Should the sexual

dysfunction be reasonably attributed to the

antidepressant, both general and antidote treatments

should be considered using an individualized approach.

--- v0rnan19 wrote:

>

>

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1471-4159.2006.03750.\

> x

>

<http://www.blackwell-synergy.com/doi/abs/10.1111/j.1471-4159.2006.03750\

> .x>

>

> As I've mentioned before, I believe PSSD is caused

> by persistently

> altered cerebral gene expression. This new paper

> shows that

> antidepressants can cause quite complex changes in

> expression after only

> one month of use in rats. Almost 100 genes were

> effected.

>

> Vornan

>

>

Kind Regards

Stuart

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