Article Type: Original Articles
SSRI Induced Apathy Syndrome
Elcin Ozsin Aydemir, Eda Aslan, Mustafa Kemal Yazici
Objective: Apathy is defined as diminished motivation and reduced goal-directed behavior accompanied by decreased emotional responsiveness. Besides being a symptom of some neurological conditions and psychiatric disorders, apathy is also a known to be an adverse effect of antidepressants. Although attention to antidepressant-induced apathy has been increasing in recent years, studies about apathy are still very limited and generally presented as case reports. Despite being an important cognitive side effect of antidepressants it is not well recognized and may be misinterpreted as a residual symptom of the psychiatric disorder by clinicians. In this study, we aimed to analyze apathy levels of patients with anxiety disorders (AD) and major depressive disorder (MDD) before and after antidepressant treatment, with a prospective design.

Methods: Our study included 20 MDD and 20 AD patients admitted to Mersin University Research and Training Hospital, Outpatient Clinic of Psychiatry, who have not taken any antidepressant medication for at least last one month. Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Apathy Evaluation Scale (AES) were administered before antidepressant treatment and on the 6th week of the treatment. Correlations and relationships between scale scores were analyzed.

Results: Thirty-five (87,5%) of the 40 patients were taking Selective Serotonin Reuptake inhibitors (SSRIs), while 5 (12,5%) were taking Serotonin-Noradrenalin Reuptake Inhibitors (SNRIs). In the whole group of patients, AES scores increased from a mean of 20,5 at baseline to 25 after antidepressant treatment (p<0,05). The increase in AES scores were significant only in patients taking SSRIs (p<0.001). Symptoms of depression and anxiety were improved in both patient groups. The mean HAM-D scores before and after treatment were 17,8 and 8,2 in MDD patients, respectively (p<0,05). The mean HAM-A score was 18,6 in AD patients before treatment, which decreased to a mean of 9,9 points after treatment (p<0,05).

Conclusion: Despite the reduction in depression and anxiety scores, six weeks of treatmet with SSRIs was associated with the development of apathy in our study group, consisting of patients with MDD or AD. Clinicians should bear in mind that apathy is likely to occur within weeks of SSRI treatment and screen for it during the course of treatment.

Key words: Anxiety disorder, apathy, major depressive disorder, SSRI, SNRI, side effect
Psychiatry and Behavioral Sciences 2018;8(2):63-70
1. Marin RS, Wilkosz PA. Disorders of diminished motivation. J Head Trauma Rehabil 2005;20(4):377-88.

2. Barnhart WJ, Makela EH, Latocha MJ. SSRI-induced apathy syndrome: a clinical review. J Psychiatr Pract 2004;10(3):196-9.

3. Spitzer RL, Williams JBW, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID): I: History, Rationale, and Description. Arch Gen Psychiatry 1992;49(8):624-9.

4. Ozkurkcugil A, Aydemir O, Yildiz M, Esen Danaci A, Koroglu E. Structured clinical interview for DSM-IV axis I disorders-clinical version in Turkish: study of reliability. Ilac ve Tedavi Dergisi 1999;12(4):233-236. (Turkish)

5. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.

6. Williams JB. A structured interview guide for the Hamilton Depression Rating Scale. Arch Gen Psychiatry 1988;45(8):742-7.

7. Akdemir A, Turkcapar MH, Orsel SD, Demirergi N, Dag I, Ozbay MH. Reliability and validity of the Turkish version of the Hamilton Depression Rating Scale. Compr Psychiatry 2001;42(2):161-5.

8. Maier W, Buller R, Philipp M, Heuser I. The Hamilton Anxiety Scale: reliability, validity and sensitivity to change in anxiety and depressive disorders. J Affect Disord 1988;14(1):61-8.

9. Yazici MK, Demir B, Tanriverdi N, Karaagaoglu E, Yolac P. Hamilton anxiety rating scale: interrater reliability and validity study. Turk Psikiyatri Derg 1998:9(2);114-7.

10. Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of the apathy evaluation scale. Psychiatry Res 1991;38(2):143-62.

11. Gulseren S, Atun C, Erol A, Aydemir O, Celebisoy M, Kultur S. The validity and reliability study of the Apati Evaluation Scale-Turkish version. Arch Neuropsychiatry 2001;38(3):142-50.

12. Bolling MY, Kohlenberg RJ. Reasons for Quitting Serotonin Reuptake Inhibitor Therapy: Paradoxical Psychological Side Effects and Patient Satisfaction. Psychother Psychosom 2004;73(6):380-5.

13. Hu XH, Bull SA, Hunkeler EM, Ming E, Lee JY, Firteman B, et al. Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: Patient report versus physician estimate. J Clin Psychiatry 2004;65(7):959-65.

14. Papakostas GI. Cognitive symptoms in patients with major depressive disorder and their implications for clinical practice. J Clin Psychiatry 2014;75(1):8-14.

15. Kelly K, Posternak M, Alpert JE. Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10(4):409-18.

16. Fava M, Graves LM, Benazzi F, et al. A cross-sectional study of the prevalence of cognitive and physical symptoms during long-term antidepressant treatment. J Clin Psychiatry 2006;67(11):1754-9.

17. De Berardis D, Valchera A, Fornaro M, Serroni N, Marini S, Moschetta FS, et al. Agomelatine reversal of escitalopram-induced apathy: a case report. Psychiatry Clin Neurosci 2013;67(3):190-1.

18. De Deurwaerdère P, Di Giovanni G. Serotonergic modulation of the activity of mesencephalic dopaminergic systems: Therapeutic implications. Prog Neurobiol 2017;151:175-236.

19. Wise RA. Forebrain substrates of reward and motivation. J Comp Neurol 2005;493(1):115-21.

20. Callegari I, Mattei C, Benassi F, Krueger F, Grafman J, Yaldizli O, et al. Agomelatine improves apathy in frontotemporal dementia. Neurodegener Dis 2016;16(5-6):352-6.

21. Serretti A, Calati R, Goracci A, Di Simplicio M, Castrogiovanni P, De Ronchi D. Antidepressants in healthy subjects: what are the psychotropic/psychological effects? Eur Neuropsychopharmacol 2010;20(7):433-53.

22. Taylor MJ, Godlewska BR, Norbury R, Selvaraj S, Near J, Cowen PJ. Early increase in marker of neuronal integrity with antidepressant treatment of major depression: 1H-magnetic resonance spectroscopy of N-acetyl-aspartate. Int J Neuropsychopharmacol 2012;15(10):1541-6.

23. Harmer CJ, O’Sullivan U, Favaron E, Massey-Chase R, Ayres R, Reinecke A, et al. Effect of acute antidepressant administration on negative affective bias in depressed patients. Am J Psychiatry 2009;166(10):1178-84.

24. Padala PR, Padala KP, Monga V, Ramirez DA, Sullivan DH. Reversal of SSRI-associated apathy syndrome by discontinuation of therapy. Ann Pharmacother 2012;46(3):e8.

25. Sato S, Asada T. Sertraline-induced apathy syndrome. J Neuropsychiatry Clin Neurosci 2011;23(1):E19.

26. Marin RS, Firinciogullari S, Biedrzycki RC. The sources of convergence between measures of apathy and depression. J Affect Disord 1993;28(1):7-14.

27. Price J, Cole V, Goodwin GM. Emotional side-effects of selective serotonin reuptake inhibitors: qualitative study. Br J Psychiatry 2009;195(3):211-7.
Online ISSN: 2636-834X
Creative Commons License This work is licensed under a Creative Commons Attribution 3.0 Unported License