Second generation antidepressants: non –responder patients and adverse drug reactions

19 February 2012

Lester [1]wrote in an editorial about use, efficacy and tolerability of newer antidepressants. I think some points should be added. There is an increase of polypharmacy in psychiatric patients. Rüther et al.[2]) observed that only thirty percent of depressed in-patients recieved one single antidepressant. The problems with drug interactions are increasing. Different antidepressant subgroups (SSRI, SNRI vs. older,tricyclic antidepressants) differed significantly in their side effect profiles but not in their incidences. Severe adverse drug reactions associated with second generation antidepressants are important limitations. Sexual dysfunctions are common [3]. The risks of (gastrointestinal) bleedings [4) and osteoporosis and nonvertebral fractures (especially in older patients) [5] are high. Suicidal ideations [6] associated with SSRI remain unclear in (younger) depressed patients and are discussed in public [7]. Further problems are QTc prolongation in treatment with citalopram and escitalopram [8] and SSRI withdrawal. The development of an intensive discussion of the comparision of older vs. newer antipsychotics (CATIE :Clinical Antipsychotic Trials of Intervention Effectiveness) and CUtLASS :Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study[9]) and in clinical trials without sponsorship by industry should be of interest in the use of second generation antidepressants. There is no single antidepressant that is best for every depressed patient. Guidelines may be important [10), but implications for clinicians with an individualized treatment still remains complex (non-responder).
1)Lester H. Choosing a second generation antidepressant for treatment of major depressive disorder.BMJ 2012; 344 doi: 10.1136/bmj.e1014
2) Rüther, E., Grohmann, R., Degner D, Gruber-Rüther, A., Loosen, P. Drug Surveillance in Psychiatry: Update on Antidepressants. Abstract, ACNP-Meeting, 2007
3)Reid S, Barbui C.Long term treatment of depression with selective serotonin reuptake inhibitors and newer antidepressants.BMJ 2010 ;26;340:c1468.
4) Andrade C, Sandarsh S, Chethan KB, Nagesh KS.Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry 2010;71(12):1565-75
5) Ziere G, Dieleman JP, van der Cammen TJ, Hofman A, Pols HA, Stricker BH.Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008;28(4):411-7
6) Goldsmith L, Moncrieff J.The psychoactive effects of antidepressants and their association with suicidality. Curr Drug Saf. 2011;6(2):115-21
7) Hernandez JF, Mantel-Teeuwisse AK, van Thiel GJ, Belitser SV, Raaijmakers JA, Pieters T.Publication trends in newspapers and scientific journals for SSRIs and suicidality: a systematic longitudinal study. BMJ Open. 2011 Dec 6;1(2):e000290. Print 2011.
8) Howland RH.A critical evaluation of the cardiac toxicity of citalopram: part 1. J Psychosoc Nurs Ment Health Serv. 2011;49(11):13-6
9)Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, Murray RM, Markwick A, Lewis SW).Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1).Arch Gen Psychiatry. 2006;63(10):1079-87.
10)National Institute for Health and Clinical Excellence. The treatment and management of depression in adults (update). (Clinical guideline 90.) 2009. http://guidance.nice.org.uk/CG90

Competing interests: None declared

Detlef Degner, psychiatrist

University of Göttingen, Germany, Department of Psychiatry and Psychotherapy, D-37073 Göttingen, Germany

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