Prediction of Antidepressant Response to Venlafaxine by a Combination of Early Response Assessment and Therapeutic Drug Monitoring

 

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Abstract

Introduction:  Early assessment of a therapeutic response is a central goal in antidepressant treatment. The present study examined the potential for therapeutic drug monitoring and symptom rating to predict venlafaxine treatment efficacy (measured by overall patient response and remission).

Methods:  88 patients were uptitrated homogenously to 225 mg/day venlafaxine. Serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) were measured at week 2. Continuous psychopathometric ratings were measured for up to 6 weeks by independent study raters.

Results:  An early improvement was significantly more common in venlafaxine responders than non-responders (χ²; p=0.007). While ODV serum levels were significantly higher in responders (t test; p=0.006), VEN serum levels, sum level of VEN+ODV and the ratio of ODV/VEN levels were not. Moreover, patients who showed an early response combined with an ODV serum level above the median of 222 ng/mL were significantly more likely to achieve full response (binary logistic model; p<0.01). Sensitivity (84% for early response) and specificity (81% for combination of early response and therapeutic drug monitoring) were sufficient to qualify as a reasonable screening instrument.

Conclusion:  Our results indicate that early improvement and ODV serum concentration are predictive of therapeutic outcome and can thus be used to guide use of the antidepressant venlafaxine.

• References

• 1 Adli M, Berghofer A, Linden M et al. Effectiveness and feasibility of a standardized stepwise drug treatment regimen algorithm for inpatients with depressive disorders: Results of a 2-year observational algorithm study. J Clin Psychiatry 2002; 63: 782-790
  Google Scholar
• 2 Adli M, Wiethoff K, Baghai T et al. Algorithm guided treatment of depression compared to treatment as usual – results from the randomized multicenter. German Algorithm Project 3 Submitted
  PubMedGoogle Scholar
• 3 Bauer M, Pfennig A, Linden M et al. Efficacy of an algorithm-guided treatment compared with treatment as usual: a randomized, controlled study of inpatients with depression. J Clin Psychopharmacol 2009; 29: 327-333
  Google Scholar
• 4 Rush AJ, Fava M, Wisniewski SR et al. for the STAR*D Investigators Group . Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design. Con Clin Trials 2003; 25: 119-142
  PubMedGoogle Scholar
• 5 Trivedi MH, Rush AJ, Crismon ML et al. Clinical results for patients with major depressive disorder in the Texas Medication Algorithm Project. Arch Gen Psychiatry 2004; 26: 457-494
  PubMedGoogle Scholar
• 6 Nakajima S, Suzuki T, Watanabe K et al. Accelerating response to antidepressant treatment in depression: a review and clinical suggestions. Prog Neuropsychopharmacol Biol Psychiatry 2010; 61: 669-680
  PubMedGoogle Scholar
• 7 Szegedi A, Muller MJ, Anghelescu I et al. Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression. J Clin Psychiatry 2003; 64: 413-420
  CrossrefPubMedGoogle Scholar
• 8 Szegedi A, Jansen WT, van Willigenburg AP et al. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry 2009; 70: 344-353
  CrossrefPubMedGoogle Scholar
• 9 Adli M, Baethge C, Heinz A et al. Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review. Eur Arch Psychiatry Clin Neurosci 2005; 255: 387-400
  CrossrefPubMedGoogle Scholar
• 10 Hiemke C, Baumann P, Bergemann N et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry 2011; 4: 195-235
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Ostad Haji E, Tadic A, Wagner S et al. Association between citalopram serum levels and clinical improvement of patients with major depression. J Clin Psychopharmacol 2011; 31: 281-286
  CrossrefPubMedGoogle Scholar
• 12 Montgomery SA. Rapid onset of action of venlafaxine. Int Clin Psychopharmacol 1995; 10 (Suppl. 02) 21-27
  PubMedGoogle Scholar
• 13 Katz MM, Meyers AL, Prakash A et al. Early symptom change prediction of remission in depression treatment. Psychopharmacol Bull 2009; 42: 94-107
  PubMedGoogle Scholar
• 14 Liebowitz MR, Tourian KA. Efficacy, safety, and tolerability of Desvenlafaxine 50 mg/d for the treatment of major depressive disorder: a systematic review of clinical trials. Prim Care Companion J Clin Psychiatry 2010; 12 DOI: 10.4088/PCC.09r00845blu.
  PubMedGoogle Scholar
• 15 Deecher DC, Beyer CE, Johnston G et al. Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther 2006; 318: 657-665
  CrossrefPubMedGoogle Scholar
• 16 Veefkind AH, Haffmans PM, Hoencamp E. Venlafaxine serum levels and CYP2D6 genotype. Ther Drug Monit 2000; 22: 202-208
  CrossrefPubMedGoogle Scholar
• 17 Reis M, Lundmark J, Bjork H et al. Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting. Ther Drug Monit 2002; 24: 545-553
  CrossrefPubMedGoogle Scholar
• 18 Hinrichs JW, Loovers HM, Scholten B et al. Semi-quantitative CYP2D6 gene doses in relation to metabolic ratios of psychotropics. Eur J Clin Pharmacol 2008; 64: 979-986
  CrossrefPubMedGoogle Scholar
• 19 van der Weiden J, Baalen-Benedek EH, Kootstra-Ros JE. Metabolic ratios of psychotropics as indication of cytochrome P450 2D6/2C19 genotype. Ther Drug Monit 2005; 27: 478-483
  CrossrefPubMedGoogle Scholar
• 20 Preskorn SH, Kane CP, Lobello K et al. Cytochrome P450 2D6 phenoconversion is common in patients being treated for depression: implications for personalized medicine. J Clin Psychiatry 2013; 74: 614-621
  CrossrefPubMedGoogle Scholar
• 21 Whyte EM, Romkes M, Mulsant BH et al. CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly. Int J Geriatr Psychiatry 2006; 21: 542-549
  CrossrefPubMedGoogle Scholar
• 22 Unterecker S, Hiemke C, Greiner C et al. The effect of age, sex, smoking and co-medication on serum levels of venlafaxine and O-desmethylvenlafaxine under naturalistic conditions. Pharmacopsychiatry 2012; 45: 229-235
  Article in Thieme ConnectPubMedGoogle Scholar
• 23 Murrell MD, Cruz DA, Javors MA et al. Distribution of venlafaxine, O-desmethylvenlafaxine, and O-desmethylvenlafaxine to venlafaxine ratio in postmortem human brain tissue. J Forensic Sci 2014; 59: 683-689
  CrossrefPubMedGoogle Scholar
• 24 Tadić A, Gorbulev S, Dahmen N et al. the EMC Study Group . Rationale and design of the randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with Major Depressive Disorder – the EMC trial. Trials 2010; 11: 21 Published online DOI: 10.1186/1745-6215-11-21.
  CrossrefPubMedGoogle Scholar
• 25 Nakajima S, Uchida H, Suzuki T et al. Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial. Prog Neuropsycho­pharmacol Biol Psychiatry 2011; 35: 1983-1989
  PubMedGoogle Scholar