Use of bupropion in combination with serotonin reuptake inhibitors.
ABSTRACT Incomplete symptom remission and sexual side effects are common problems for which bupropion often is added to treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs) for patients with major depressive disorder (MDD). This article reviews the literature on combining bupropion with SSRIs or SNRIs. We used MEDLINE to select studies that included patients diagnosed with MDD treated with any combination of bupropion and an SSRI or SNRI, either to enhance antidepressant response or to ameliorate antidepressant-associated sexual dysfunction. Bibliographies of located articles were searched for additional studies. Controlled and open-label studies support the effectiveness of bupropion in reversing antidepressant-associated sexual dysfunction, whereas open trials suggest that combination treatment with bupropion and an SSRI or SNRI is effective for the treatment of MDD in patients refractory to the SSRI, SNRI, or bupropion alone. The available data suggest that, although not an approved indication, the combination of bupropion and either an SSRI or an SNRI is generally well tolerated, can boost antidepressant response, and can reduce SSRI or SNRI-associated sexual side effects. Additional randomized controlled studies are needed to answer important questions, such as those regarding optimal dose and duration of treatment.
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ABSTRACT: Venlafaxine is recognised as an effective treatment for depression and is known to inhibit the reuptake of serotonin (5-HT) and noradrenaline (NA). Another antidepressant, bupropion, acts to inhibit dopamine (DA) and NA reuptake and is commonly co-administered with other antidepressants to improve the efficacy of the antidepressant effect. The present study was designed to investigate the acute effect of combining the 2 drugs on extracellular levels of 5-HT, DA, and NA in rat frontal cortex using brain microdialysis, with the drugs being administered by intraperitoneal injection (i.p). Bupropion (10 mg/kg body mass, i.p.) alone had no effect on extracellular 5-HT levels, whereas venlafaxine (10 mg/kg, i.p.) alone significantly elevated extracellular 5-HT over basal values. As expected, bupropion alone elevated extracellular dopamine above basal values at 40 min post-drug administration, and this effect lasted for a further 2 h. Venlafaxine alone did not statistically elevate extracellular dopamine. The co-administration of venlafaxine with bupropion resulted in a dramatic increase in extracellular dopamine, and this effect was significantly greater than that seen with bupropion alone. In the frontal cortex, NA was elevated by bupropion alone and venlafaxine alone, relative to the control animals. The combination of bupropion and venlafaxine resulted in a marked elevation of NA.Canadian Journal of Physiology and Pharmacology 04/2012; 90(6):803-9. DOI:10.1139/y2012-045 · 1.55 Impact Factor
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ABSTRACT: Sexual dysfunction (SD) is a frequently reported side-effect of antidepressant treatment, particularly of selective serotonin reuptake inhibitors (SSRIs). In the multicentre clinical and pharmacogenetic GENDEP study (Genome-based Therapeutic Drugs for Depression), the effect of the serotonin transporter gene promoter polymorphism 5-HTTLPR on sexual function was investigated during treatment with escitalopram (SSRI) and nortriptyline (tricyclic antidepressant). A total of 494 subjects with an episode of DSM-IV major depression were randomly assigned to treatment with escitalopram or nortriptyline. Over 12 weeks, depressive symptoms and SD were measured weekly with the Montgomery-Asberg Depression Rating Scale, the Antidepressant Side-Effect Checklist, the UKU Side Effect Rating Scale, and the Sexual Functioning Questionnaire. The incidence of reported SD after 12 weeks of treatment was relatively low, and did not differ significantly between antidepressants (14.9% escitalopram, 19.7% nortriptyline). There was no significant interaction between the 5-HTTLPR and antidepressant on SD. Improvement in depressive symptoms and younger age were both associated with lower SD. The effect of age on SD may have been moderated by the 5-HTTLPR. In GENDEP, rates of reported SD during treatment were lower than those described in previous reports. There was no apparent effect of the 5-HTTLPR on the observed decline in SD.The World Journal of Biological Psychiatry 03/2011; 12(7):528-38. DOI:10.3109/15622975.2011.559270 · 4.23 Impact Factor
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ABSTRACT: Triple reuptake inhibitors (TRIs) that block the dopamine transporter (DAT), norepinephrine transporter, and serotonin transporter are being developed as a new class of antidepressant that may have better efficacy and fewer side effects compared with traditional antidepressants. We describe a novel TRI, 2-[4-(4-chlorophenyl)-1-methylpiperidin-3-ylmethylsulfanyl]-1-(3-methylpiperidin-1-yl)-ethanone (JZAD-IV-22), that inhibits all three monoamine transporters with approximately equal potency in vitro. (+/-)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.1.0]hexane hydrochloride (DOV 216,303), a TRI shown to be an effective antidepressant in a clinical trial, shows reuptake inhibition similar to that of JZAD-IV-22 in vitro. Furthermore, both JZAD-IV-22 and DOV 216,303 increase levels of dopamine, norepinephrine, and serotonin in the mouse prefrontal cortex when administered by peripheral injection. JZAD-IV-22 and DOV 216,303 exhibited antidepressant-like efficacy in the mouse forced-swim and tail-suspension tests at doses that increased neurotransmitter levels. Because development of DAT inhibitors could be hindered by abuse liability, both JZAD-IV-22 and DOV 216,303 were compared in two assays that are markers of abuse potential. Both JZAD-IV-22 and DOV 216,303 partially substituted for cocaine in a drug discrimination assay in rats, and high doses of DOV 216,303 produced locomotor sensitization in mice. JZAD-IV-22 showed no evidence of sensitization at any dose tested. These results demonstrate that JZAD-IV-22 is a TRI with antidepressant-like activity similar to that of DOV 216,303. The striking feature that distinguishes the two TRIs is that locomotor sensitization, a common underlying feature of drugs of abuse, is seen with DOV 216,303 but is completely lacking in JZAD-IV-22. These findings may have implications for the potential for abuse liability in humans.Journal of Pharmacology and Experimental Therapeutics 12/2010; 335(3):762-70. DOI:10.1124/jpet.110.174011 · 3.86 Impact Factor