SSRIs Zolpidem

Depressed individuals effectively treated with SSRIs often report persistent insomnia and require adjunctive sleep-promoting therapy. A study of the efficacy of zolpidem in this patient population showed that a dose of 10 mg was effectively and safely coadministered with an SSRI, resulting in improved self-rated sleep, daytime functioning, and well-being (150). 

Asnis GM, Chakraburtty A, DuBoff EA, et al. Zolpidem for persistent insomnia in SSRI-treated depressed patients. J Clin Psychiatry 1999 60 668-676. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Insomnia is a common comorbid condition with depression, and frequently is made worse by antidepressants, particularly the SSRIs. When insomnia persists despite adequate evaluation and attempts to reduce it by other approaches, it is often necessary to use a concomitant sedative-hypnotic, especially a short-acting nonbenzodiazepine with rapid onset such as zaleplon or zolpidem. At times a benzodiazepine sedative hypnotic such as triazolam or temazepam may be necessary. If anxiety persists during the day and cannot be otherwise managed, it may be necessary to add an anxiolytic benzodiazepine such as alprazolam or clonazepam. Use of sedative-hypnotics and anxiolytics should be short-term whenever possible. 

Drug combinations Probably the most common combination treatment is concomitant use of an SSRI and a benzodiazepine, especially on initiation of treatment (Fig. 9—6). The benzodiazepines (especially alprazolam and clonazepam) not only appear to act synergistically to increase the onset of therapeutic action and perhaps even boost the efficacy of SSRIs, but they also appear to block the anxiogenic actions of the SSRIs and lead to better tolerability as well as the ability to attain therapeutic dosing levels for the SSRIs. Sometimes sedative-hypnotics such as zale-plon or zolpidem are required in addition to an SSRI, especially on initiation of SSRI treatment. 

With respect to a specific and common clinical problem, advice to withdraw hypnotic medication should follow a careful evaluation of self-reported sleep patterns, psychological factors and psychosocial status. Ambulant monitoring can be helpful in patients who have encountered severe problems in effecting withdrawal. A careful psychiatric assessment should be made to ascertain whether the patient has clinically significant anxiety and/or depression. Both should be treated with a selective serotonin receptor inhibitor (SSRI) before withdrawal from the hypnotic is attempted. An optimal tapering schedule should be discussed with the patient some will attempt a rapid withdrawal over less than 8 weeks and others will require much longer. This is particularly so if previous attempts to withdraw have been unsuccessful. Carers, family and friends should be mobilized to help in withdrawal, should the patient wish this. Substitution of zolpidem may facilitate withdrawal but should be kept as a reserve strategy. 

The authors speculated that the combination of zolpidem with an SSRI might have predisposed to the serotonin syndrome. It is also possible that some people (for example poor metabolizers) are idiosyncratically vulnerable to serotonin toxicity at low doses of SSRIs. 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

Some SSRIs (notably fluvoxamine and to a lesser extent fluoxetine) and their metabohtes inhibit hepatic oxidative enzymes, particularly CYP2C19 and CYP3A, that metabolize most benzodiazepines, as well as zaleplon, zolpidem, zopiclone, and buspirone (SEDA-22, 39) (SEDA-22, 41) (168,169). Apart from fluvoxamine, SSRIs do not generally have a chnically prominent effect on hypnosedative effects studies vary from those that have found that fluoxetine has a moderate but functionally unimportant impact on diazepam concentrations (170) to results that suggest significant aggravation of the cognitive effects of alprazolam when co-prescribed with the SSRI (171). 

There is some evidence to suggest that the metabolism of some benzodiazepines (such as alprazolam, bromazepam, diazepam, and also possibly midazolam, nitrazepam and triazolam) may be reduced by some SSRIs (such as fluoxetine and fluvoxamine). On the whole, no clinically significant interaction appears to occur between other SSRIs and the benzodiazepines or related dri s such as cloral hydrate or zaleplon. There is some evidence to support the su estion that sedation is likely to be increased by the concurrent use of SSRIs and benzodiazepines. Rare cases of hallucinations have been seen with zolpidem and some SSRb. Symptoms of the serotonin syndrome have been reported in two patients taking paroxetine and a benzodiazepine. 

However, a pharmacodynamic interaction may occur. Hallucinations have been seen with zolpidem alone, and they have also occurred, rarely, when zolpidem and some benzodiazepines were given with the SSRIs , (below), which are related to venlafaxine. However, adverse effects such as these seem rare and the concurrent use of these drugs need not be avoided, but bear this possible interaction in mind if hallucinations occur. 

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