• Leigh Jennings


Identifying and treating depression are integral to the care of the neurology patient. First-line, evidence-based treatments for depression include antidepressant medication and depression-focused psychotherapy. All antidepressants are considered equally effective; therefore most clinicians select an agent based upon its side effect and safety profile. An antidepressant must be given at its therapeutic dose for 4–6 weeks before determining whether it is working. Escitalopram and sertraline are well-tolerated SSRIs with few drug-drug interactions. Common side effects of antidepressants include nausea, feeling jittery, weight gain, and sexual dysfunction. Clinicians should be vigilant for less common but more worrisome events such as treatment-emergent akathisia, suicidality, or a hypomanic or manic episode. The use of antidepressants in specific neurological illnesses is also discussed. Self-report scales for measuring treatment responses are reviewed.


Antidepressants Major depressive disorder Depression Dysthymia Persistent depressive disorder Escitalopram Citalopram Sertraline Venlafaxine Duloxetine Bupropion Mirtazapine Amitriptyline Psychotherapy 


  1. 1.
    Fink P, Hansen MS, Sondergaard L, Frydenberg M. Mental illness in new neurological patients. J Neurol Neurosurg Psychiatry. 2003;74:817–9.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Thielscher C, Thielscher S, Kostev K. The risk of developing depression when suffering from neurological diseases. Ger Med Sci. 2013;11:Doc02.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Luoni C, Bisulli F, Canevini MP, De Sarro G, Fattore C, Galimberti CA, et al. Determinants of health-related quality of life in pharmacoresistant epilepsy: results from a large multicenter study of consecutively enrolled patients using validated quantitative assessments. Epilepsia. 2011;52(12):2181–91.PubMedCrossRefGoogle Scholar
  4. 4.
    Fernández-Jiménez E, Arnett P. Impact of neurological impairment, depression, cognitive function and coping on quality of life of people with multiple sclerosis: a relative importance analysis. Mult Scler. 2015;21(11):1468–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Schrag A. Quality of life and depression in Parkinson’s disease. J Neurol Sci. 2006;248(1–2):151–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Carson AJ, Ringbauer B, Mackenzie L, Warlow C, Sharpe M. Neurological disease, emotional disorder, and disability: they are related: a study of 300 consecutive new referrals to a neurology outpatient department. J Neurol Neurosurg Psychiatry. 2000;68:202–6.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Chemerinski E, Robinson RG, Arndt S, Kosier JT. The effect of remission of poststroke depression on activities of daily living in a double-blind randomized treatment study. J Nerv Ment Dis. 2001;189:421–5.PubMedCrossRefGoogle Scholar
  8. 8.
    DiMatteo RM, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med. 1997;12:439–45.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Mohr DC, Hart SL, Julian L, et al. Screening for depression among patients with multiple sclerosis: two questions may be enough. Mult Scler. 2007;13:215–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Manea L, Gilbody S, Hewitt C, North A, Plummer F, Richardon R, et al. Identifying depression with the PHQ-2: a diagnostic meta-analysis. J Affect Disord. 2016;203:382–95. The sensitivity of the PHQ-2 using a cutoff of 2 in primary care is 0.91PubMedCrossRefGoogle Scholar
  12. 12.
    Mitchell AJ, Yadagarfar M, Gill J, Stubbs B. Case finding and screening clinical utility of the Patient Health Questionnaire (PHQ-2 and PHQ-9) for depression in primary care: a diagnostic meta-analysis of 40 studies. B J Psychiatry Open. 2016;2:127–38.CrossRefGoogle Scholar
  13. 13.
    Topp CW, Ostergaard SD, Songergaard S, Bech P. The WHO-5 well-being index: a systematic review of the literature. Psychother Psychosom. 2015;84:167–76.PubMedCrossRefGoogle Scholar
  14. 14.
    Wancata J, Alexandrowicz R, Marquart B, Weiss M, Frederich F. The criterion validity of the geriatric depression scale: a systematic review. Acta Psychiatr Scand. 2006;114:398–410. The sensitivity of the GDS-30 is 0.753 and the specificity is 0.770. The sensitivity of the GDS-15 is 0.805 and the specificity is 0.750PubMedCrossRefGoogle Scholar
  15. 15.
    Chakkamparambil B, Chibnall JT, Graypel EA, Manepalli JN, Bhutto A, Grossberg GT. Development of a brief validated geriatric screening tool: the SLU “AM SAD”. Am J Ger Psych. 2015;23(8):780–3. The sensitivity of the AM SAD in this study is 0.75 and the specificity is 0.62CrossRefGoogle Scholar
  16. 16.
    Fragoso YD, Adoni T, Anacleto A, da Gama D, Goncalves MVM, Palma da Cunha Matta P, et al. Recommendations on diagnosis and treatment of depression and anxiety in patients with multiple sclerosis. Pract Neurol. 2014;0:1–6. *Recommended readingGoogle Scholar
  17. 17.
    Marsh L. Depression and Parkinson’s disease: current knowledge. Curr Neurol Neurosci Rep. 2013;13(12):409. *Recommended readingPubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Cuijpers P, Smit F, van Straten A. Psychological treatments of subthreshold depression: a meta-analytic review. Acta Psychiatr Scand. 2007;115(6):434–41.PubMedCrossRefGoogle Scholar
  19. 19.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013. p. 168–71.CrossRefGoogle Scholar
  20. 20.
    Kriston L, von Wolff A, Westphal A, Hölzel LP, Härter M. Efficacy and acceptability of acute treatments for persistent depressive disorder. Depress Anxiety. 2014;31:621–30.PubMedCrossRefGoogle Scholar
  21. 21.
    Jobst A, Brakemeier EL, Buchheim A, Caspar F, Cuijpers P, Ebmeier KP, et al. European psychiatric association guidance on psychotherapy in chronic depression across Europe. Eur Psychiatry. 2016;33:18–36.PubMedCrossRefGoogle Scholar
  22. 22.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013. p. 160–8.CrossRefGoogle Scholar
  23. 23.
    American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. Arlington: American Psychiatric Association; 2010.Google Scholar
  24. 24.
    National Institute for Health and Care Excellence (NICE). Depression in adults with a chronic physical health problem: recognition and management. London: NICE; 2009.Google Scholar
  25. 25.
    Fournier JC, RJ DR, Hollon SD, Dimidjian S, Amsterdam JD, Sheldon RC, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010;303:47–53. The effect size for mild depression was 0.11 and for moderate depression, 0.17PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008;5(2):e45.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Vöhringer PA, Ghaemi SN. Solving the antidepressant efficacy question: effect sizes in major depressive disorder. Clin Ther. 2011;33(12):B49–61.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Kanner AM. Management of psychiatric and neurological comorbidities in epilepsy. Nat Rev Neurol. 2016;12:106–16.PubMedCrossRefGoogle Scholar
  29. 29.
    Hawton K, Casanas I, Comabella C, Haw C, Saunders K. Risk factors for suicide in individuals with depression: a systematic review. J Affect Disord. 2013;147(1):17–28.PubMedCrossRefGoogle Scholar
  30. 30.
    American Psychiatric Association. Guideline III. Assessment of suicide risk. In: Practice guidelines for the psychiatric evaluation of adults, 3rd ed. Arlington: American Psychiatric Association; 2015.
  31. 31.
    Lam RW. Onset, time course and trajectories of improvement with antidepressants. Eur Neuropsychopharmacol. 2012;22(Suppl 3):S492–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Sacchetti E, Conte G, Guarneri L. Are SSRI antidepressants a clinically homogenous class of compounds? Lancet. 1994;344(8915):126–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Schatzberg A, Debattista C. Manual of clinical psychopharmacology. 8th ed. Arlington: American Psychiatric Publishing; 2015.CrossRefGoogle Scholar
  34. 34.
    Lexapro ®(escitalopram oxalate). [package insert from internet]. Irvine: Allergan USA., 2016. [revised Jan 2017; cited 20 Mar 2017]. Available from:
  35. 35.
    Sheeler RD, Ackerman MJ, Richelson E, Nelson TK, Staab JP, Tangalos EG, et al. Considerations on safety concerns about citalopram prescribing. Mayo Clin Proc. 2012;87(11):1042–5.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Medicines and Healthcare Products Regulatory Agency (MHRA). Citalopram and escitalopram: QT interval prolongation—new maximum daily dose restrictions (including in elderly patients), contraindications, and warnings. Drug Saf Updat. 2011;5:A1.Google Scholar
  37. 37.
    US Food and Drug Administration. FDA drug safety communication: revised recommendations for Celexa (citalopram hydrobromide) related to a potential for abnormal heart rhythms with high doses. March 8, 2012. Accessed on 1 Jan 2017:
  38. 38.
    Celexa® (citalopram hydrobromide). [package insert from internet]. St. Louis: Forest Laboratories., July 8, 2014. Accessed on 1 Jan 2017:
  39. 39.
    Shapiro PA, Lesperance F, Frasure-Smith N, O’Connor CM, Baker B, Jiang JW, et al. An open-label preliminary trial of sertraline for treatment of major depression after acute myocardial infarction (the SADHAT trial). Sertraline Anti-Depressant Heart Attack trial. Am Heart J. 1999;137:1100–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Zoloft® (sertraline hydrochloride). [package insert from internet]. New York: Pfizer, 2016. [revised Oct 2016; cited 23 Dec 2016]. Available from:
  41. 41.
    Aiyer R, Barkin RL, Bhatia A. Treatment of neuropathic pain with venlafaxine: a systematic review. Pain Med. 2016;00:1–14.Google Scholar
  42. 42.
    Joffe H, Guthrie KA, LaCroix AZ, Reed SD, Ensrud KE, Manson JE. Randomized controlled trial of low-dose estradiol and the SNRI venlafaxine for vasomotor symptoms. JAMA Intern Med. 2014;174(7):1058–66.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Ozyalcin SN, Talu GK, Kiziltan E, Yucel B, Ertas M, Disci R. The efficacy and safety of venlafaxine in the prophylaxis of migraine. Headache. 2005;45:144–52.PubMedCrossRefGoogle Scholar
  44. 44.
    Effexor®(venlafaxine hydrochloride tablets). [package insert from internet]. Philadelphia: Wyeth Pharmaceuticals; 2015. [revised Feb 2015; cited 1 Jan 2017.] Available at:
  45. 45.
    Cymbalta® (duloxetine hydrochloride oral capsule, delayed release pellets). [package insert from internet]. Indianapolis: Eli Lilly; 2008. [revised 13 June 2008; cited 1 Jan 2017]. Available at:
  46. 46.
    Patroneva A, Connolly SM, Fatato P, Pederson R, Jiang Q, Guico-Pabia C, et al. An assessment of drug-drug interactions: the effect of desvenlafaxine and duloxetine on the pharmacokinetics of the CYP2D6 probe desipramine in healthy subjects. Drug Metab Dis. 2008;36:2484–91.CrossRefGoogle Scholar
  47. 47.
    Zyban® (bupropion hydrochloride sustained-release tablets). [package insert on the internet]. Research Triangle Park: GlaxoSmithKline; 2016. [revised June 2016; cited 1 Jan 2017]. Available from:
  48. 48.
    Jefferson JW, Pradko JF, Muir KT. Bupropion for major depressive disorder: pharmacokinetic and formulations considerations. Clin Ther. 2005;27:1685–95.PubMedCrossRefGoogle Scholar
  49. 49.
    Wellbutrin XL® (bupropion hydrochloride extended release tablets). [package insert from internet]. Research Triangle Park: GlaxoSmithKline; 2016. [revised April 2016; cited 12 March 2017]. Available from:,020358s057lbl.pdf.
  50. 50.
    Croom KF, Perry CM, Plosker GL. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23:427–52.PubMedCrossRefGoogle Scholar
  51. 51.
    Lind AB, Reis M, Bengtsson F, Johnzier-Perey M, Powell Golay K, Ahlner J, et al. Steady-state concentrations of mirtazapine, N-desmethylmirtazapine, 8-hydroxymirtazapine and their enantiomers in relation to cytochrome P450 2D6 genotype, age and smoking behaviour. Clin Pharmacokinet. 2009;48:63–70.PubMedCrossRefGoogle Scholar
  52. 52.
    Remeron® (mirtazapine oral tablet). [package insert from internet]. Whitehouse Station: Merck & Co.; 2016. [revised July 2016; cited 12 March 2017]. Available at:
  53. 53.
    Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;7:CD008242.Google Scholar
  54. 54.
    Keskinbora K, Aydinli I. A double-blind randomized controlled trial of topiramate and amitriptyline either alone or in combination for the prevention of migraine. Clin Neurol Neurosurg. 2008;110:979–84.PubMedCrossRefGoogle Scholar
  55. 55.
    Taylor D, Paton C, Kapur S, editors. The Maudsley prescribing guidelines in psychiatry. 12th ed. West Sussex: Wiley; 2015.Google Scholar
  56. 56.
    Sackeim HA, Roose SP, Burt T. Length of antidepressant trials in late-life depression. J Clin Psychopharmacol. 2005;25(4 Supplement 1):S34–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Judd LL, Schettler PJ, Rush AJ, Coryell WH, Fiedorowicz JG, Solomon DA. A new empirical definition of major depressive episode recovery and its positive impact on future course of illness. J Clin Psychiatry. 2016;77(8):1065–73.PubMedCrossRefGoogle Scholar
  58. 58.
    Crismon ML, Trivedi M, Pigott TA, Rush AJ, Hirschfeld RM, Kahn DA, et al. The Texas medication algorithm project. Report of the Texas consensus conference panel on medication treatment of major depressive disorder. J Clin Psychiatry. 1999;60:142–56.PubMedCrossRefGoogle Scholar
  59. 59.
    McGrath PJ, Stewart JW, Petkova E, Quitkin FM, Amsterdam JD, Fawcett J, et al. Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression. J Clin Psychiatry. 2000;61:518–24.PubMedCrossRefGoogle Scholar
  60. 60.
    Guidi J, Tomba E, Fava GA. The sequential integration of psychotherapy and pharmacotherapy in the treatment of major depressive disorder: a meta-analysis of the sequential model and a critical review of the literature. Am J Psychiatry. 2016;173:128–37.PubMedCrossRefGoogle Scholar
  61. 61.
    Beshai S, Dobson KS, Bockting CLH, Quigley L. Relapse and recurrent prevention in depression: current research and future prospects. Clin Psychol Rev. 2011;31:1349–60.PubMedCrossRefGoogle Scholar
  62. 62.
    Qaseem A, Barry M, Kansagara D. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;164:350–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Thase ME, Greenhouse JB, Frank E, Reynolds CF, Pilkonis PA, Hurley K, et al. Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy combinations. Arch Gen Psychiatry. 1997;54:1009–15.PubMedCrossRefGoogle Scholar
  64. 64.
    Carvalho AF, Sharma MS, Brunoni AR, Vieta E, Fava GA. The safety, tolerability, and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother Psychosom. 2016;85:270–88. *Excellent review with free full text available at PubMedCrossRefGoogle Scholar
  65. 65.
    Beasley CM Jr, Sayler ME, Weiss AM, Potvin JH. Fluoxetine: activating and sedating effects at multiple fixed doses. J Clin Psychopharmacol. 1992;12(5):328–33.PubMedCrossRefGoogle Scholar
  66. 66.
    Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM. Antidepressant-induced sexual dysfunction. Ann Pharmacother. 2002;36(10):1577–89.PubMedCrossRefGoogle Scholar
  67. 67.
    Kikuchi T, Uchida H, Suzuki T, Watanabe K, Kashima H. Patients’ attitudes toward side effects of antidepressants: an internet survey. Eur Arch Psychiatry Clin Neurosi. 2011;261:103–9.CrossRefGoogle Scholar
  68. 68.
    Clayton AH, Alkis AR, Parikh NB, Votta JB. Sexual dysfunction due to psychotropic medications. Psych Clin North Am. 2016;39(3):427–63. *Helpful overview including physiology and nonpharmacologic approachesCrossRefGoogle Scholar
  69. 69.
    Taylor MJ, Rudkin L, Bullemor-Day P, Lubin J, Chukwujekwu C, Hawton K. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database Syst Rev. 2013;31(5):CD003382.Google Scholar
  70. 70.
    Fava M, Nurnberg HG, Seidman SN, Holloway W, Nicholas S, Tseng L, et al. Efficacy and safety of sildenafil in men with serotonergic antidepressant-associated erectile dysfunction: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2006;67(2):240–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Nurnberg HG, Hensley PL, Heiman JR, et al. Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial. JAMA. 2008;300(4):395–404.PubMedCrossRefGoogle Scholar
  72. 72.
    Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009;29(3):259–66.PubMedCrossRefGoogle Scholar
  73. 73.
    Blumenthal SR, Castro VM, Clements CC, Rosenfield HR, Murphy SN, Fava M, et al. An electronic health records study of long-term weight gain following antidepressant use. JAMA Psychiat. 2014;71(8):889–96.CrossRefGoogle Scholar
  74. 74.
    Fava M. Weight gain and antidepressants. J Clin Psychiatry. 2000;61(suppl 1):37–41.PubMedGoogle Scholar
  75. 75.
    Thase ME. Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry. 1998;59(10):502–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Hawthorne JM, Caley C. Extrapyramidal reactions associated with serotonergic antidepressants. Ann Pharmacoth. 2015;49(10):1136–52.CrossRefGoogle Scholar
  77. 77.
    US Food and Drug Administration. FDA proposes new warning about suicidal thinking, behavior, in young adults who take antidepressant medications. [news release] Silver Spring: US Food and Drug Administration, 2007. Accessed 1 Feb 2017 at:
  78. 78.
    Ah-kee EY, Egong E, Shafi A, Lim LT, Li Yim JF. A review of drug-induced acute angle closure glaucoma for non-ophthalmologists. Qatar Med J. 2015;6:1–8.Google Scholar
  79. 79.
    Anglin R, Yuan Y, Moayyedi P, Tse F, Armstrong D, Leontiadis GI. Serotonin reuptake inhibitors with concurrent nonsteroidal anti-inflammatory use: a systemic review and meta-analysis. Am J Gastroenterol. 2014;109:811–9. For SSRI use alone, NNH = 3,177 for low-risk patients, NNH = 881 for high-risk patients. For SSRIs and NSAIDs together, NNH = 645 for low-risk patients, NNH = 179 for high-risk patients.PubMedCrossRefGoogle Scholar
  80. 80.
    Jiang H, Chen H, Hu X, Yu Z, Yang W, Deng M, et al. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2015;13:42–50.CrossRefPubMedGoogle Scholar
  81. 81.
    Targownik LE, Bolton JM, Metge CJ, Leung S, Sareen J. Selective serotonin reuptake inhibitors are associated with a modest increase in the risk of upper gastrointestinal bleeding. Am J Gastroenterol. 2009;104(6):1475–82. Scholar
  82. 82.
    Jeong B, Kim S, Kim S, Kim J, Shin I, Yoon J. Use of serotonergic antidepressants in patients undergoing surgery. Psychosomatics. 2014;55:213–20.PubMedCrossRefGoogle Scholar
  83. 83.
    Buckley N, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626.PubMedCrossRefGoogle Scholar
  84. 84.
    FDA Alert. Combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin-norepinephrine reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. 2006. [cited 29 Jan 2017]. Available from:
  85. 85.
    Evans WR, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010;50:1089–99.PubMedCrossRefGoogle Scholar
  86. 86.
    De Picker L, Van Den Eede F, Dumont G, Moorkens G, Sabbe BG. Antidepressants and the risk of hyponatremia: a class-by-class review of literature. Psychosomatics. 2014;55(6):536–47.PubMedCrossRefGoogle Scholar
  87. 87.
    Berber MJ. FINISH: remembering the discontinuation syndrome. Flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal (anxiety/agitation). J Clin Psychiatry. 1998;59:255.PubMedCrossRefGoogle Scholar
  88. 88.
    Tint A, Haddad PM, Anderson IM. The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study. J Psychopharmacol. 2008;22(3):330–2.PubMedCrossRefGoogle Scholar
  89. 89.
    Ninan PT, Musgnung J, Messig M, Buckley G, Guico-Pabia CJ, Ramey TS. Incidence and timing of taper/posttherapy-emergent adverse events following discontinuation of desvenlafaxine 50 mg/d in patients with major depressive disorder. Prim Care Companion CNS DIsord. 2015;17(1):
  90. 90.
    Schatzberg AF, Blier P, Delgado PL, Fava M, Had-dad PM, Shelton RC. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry. 2006;67(suppl 4):27–30. [G]PubMedGoogle Scholar
  91. 91.
    Warner CH, Bobo W, Warner C, Reid S, Rachal J. Antidepressant discontinuation syndrome. Am Fam Physician. 2006;74:449–56. 457PubMedGoogle Scholar
  92. 92.
    Kerr MP, Mensah S, Besag F, de Toffol B, Ettinger A, Kanemoto K, et al. International consensus clinical practice statements for the treatment of neuropsychiatric conditions associated with epilepsy. Epilepsia. 2011;52(11):2133–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Jones JE, Hermann BP, Barry JJ, Gilliam FG, Kanner AM, Meador KJ. Rates and risk factors for suicide, suicidal ideation, and suicide attempts in chronic epilepsy. Epilepsy Behav. 2003;4:S31–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and the risk of suicide: a population-based case control study. Lancet Neurol. 2007;6:693–8.PubMedCrossRefGoogle Scholar
  95. 95.
    Alper KR, Schwartz KA, Kols RL, Khan A. Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports. Biol Psychiatry. 2007;62:345–54.PubMedCrossRefGoogle Scholar
  96. 96.
    Wellbutrin® (bupropion hydrochloride oral tablet). [package insert from internet]. Research Triangle Park: GlaxoSmithKline; 2016. [revised April 2016; cited 1 Jan 2017]. Available at:,020358s057lbl.pdf.
  97. 97.
    Spina E, Pisani F, de Leon J. Clinically significant pharmacokinetic drug interactions of antiepileptic drugs with new antidepressants and new antipsychotics. Pharmacol Res. 2016;106:72–86.PubMedCrossRefGoogle Scholar
  98. 98.
    Spaans E, van den Heuvel MW, Schnabel PG, Peeters P, Chin-Kon-Sung U, Colbers E, et al. Concomitant use of mirtazapine and phenytoin: a drug-drug interactions study in healthy male subjects. Eur J Chn Pharmacol. 2002;58:423–9.CrossRefGoogle Scholar
  99. 99.
    Sitsen J, Maris F, Timmer C. Drug-drug interaction studies with mirtazapine and carbamazepine in healthy male subjects. Eur J Drug Metab Pharmacokinet. 2001;26:109–21.PubMedCrossRefGoogle Scholar
  100. 100.
    Boinpally R, Gad N, Gupta S, Periclou A. Influence of CYP3A4 induction/inhibition on the pharmacokinetics of vilazodone. Clin Ther. 2014;36(11):1638–49.PubMedCrossRefGoogle Scholar
  101. 101.
    Ketter TA, Jenkins JB, Schroeder DH, Pazzaglia PJ, Marangell LB, George MS, et al. Carbamazepine but not valproate induces bupropion metabolism. J Clin Psychopharmacol. 1995;15:327–33.PubMedCrossRefGoogle Scholar
  102. 102.
    Gilliam FG, Barry JJ, Hermann BP, Meador KJ, Vahle V, Kanner AM. Rapid detection of major depression in epilepsy: a multicentre study. Lancet Neurol. 2006;5:399–405.PubMedCrossRefGoogle Scholar
  103. 103.
    Pontone GM, Bakker CC, Chen S, Mari Z, Marsh L, Rabins P, et al. The longitudinal impact of depression on disability in Parkinson disease. Int J Geriatr Psychiatry. 2016;31:458–65.PubMedCrossRefGoogle Scholar
  104. 104.
    Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Buyske S, et al. The impact of treatment of depression on quality of life, disability and relapse in patients with Parkinson’s disease. Move Disord. 2009;24:1325–32.CrossRefGoogle Scholar
  105. 105.
    Ravina B, Camicioli R, Como PG, Marsh L, Jankovic J, Weintraub D, et al. The impact of depressive symptoms in early Parkinson disease. Neurology. 2007;69:342–7.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Hughes TA, Ross HF, Mindham RH, Spokes EG. Mortality in Parkinson’s disease and its association with dementia and depression. Acta Neurol Scand. 2004;110:118–23.PubMedCrossRefGoogle Scholar
  107. 107.
    Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014;311(16):1670–83.PubMedCrossRefGoogle Scholar
  108. 108.
    Dyduch A, Załuska M. Depression in Parkinson’s disease: the effectiveness and risk of pharmacotherapy. Clin Rev Psychogeriatr. 2015;15:147–53.CrossRefGoogle Scholar
  109. 109.
    Barone P, Poewe W, Albrecht S, Debieuvre C, Massey D, Rascol O, et al. Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(6):573–80.PubMedCrossRefGoogle Scholar
  110. 110.
    Armento ME, Stanley MA, Marsh L, Kunik ME, York MK, Bush AL, et al. Cognitive behavioral therapy (CBT) for depression and anxiety in Parkinson’s disease: a clinical review. J Park Dis. 2012;2:135–51.Google Scholar
  111. 111.
    Schneider CB, Pilhatsch M, Rifati M, Jost WH, Wodarz F, Ebersbach G, et al. Utility of the WHO-Five Well-being Index as a screening tool for depression in Parkinson’s disease. Mov Disord. 2010;25:777–83.PubMedCrossRefGoogle Scholar
  112. 112.
    Chagas MHN, Crippa JAS, Loureiro SR, Hallak JEC, de Meneses-Gaya C, Machado-de-Sousa JP, et al. Validity of the PHQ-2 for the screening of major depression in Parkinson’s disease: two questions and one important answer. Aging Ment Health. 2011;7:838–43.CrossRefGoogle Scholar
  113. 113.
    Williams JR, Hirsch ES, Anderson K, Bush AL, Goldstein SR, Grill S, et al. A comparison of nine scales to detect depression in Parkinson disease: which scale to use? Neurology. 2012;78:998–1006.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Hackett ML, Pickles K. Part I: frequency of depression after stroke: an updated systematic review and meta-analysis of observational studies. Int J Stroke. 2014;9:1017–25.PubMedCrossRefGoogle Scholar
  115. 115.
    Robinson RG, Jorge RE. Post-stroke depression: a review. Am J Psychiatry. 2016;173:221–31.PubMedCrossRefGoogle Scholar
  116. 116.
    Kutlubaev MA, Hackett ML. Part II: predictors of depression after stroke and impact of depression on stroke outcome: an updated systematic review of observational studies. Int J Stroke. 2014;9:1026–36.PubMedCrossRefGoogle Scholar
  117. 117.
    Wei N, Yong W, Li X, et al. Post-stroke depression and lesion location: a systematic review. J Neurol. 2015;262:81–90.PubMedCrossRefGoogle Scholar
  118. 118.
    Robinson RG, Bolla-Wilson K, Kaplan E, Lipsey JR, Price TR. Depression influences intellectual impairment in stroke patients. Br J Psychiatry. 1986;148:541–7.PubMedCrossRefGoogle Scholar
  119. 119.
    Bartoli F, Lillia N, Lax A, Crocamo C, Mantero V, Carrà G, et al. Depression after stroke and risk of mortality: a systematic review and meta-analysis. Stroke Res Treat. 2013;862978.Google Scholar
  120. 120.
    Kimura M, Robinson RG, Kosier JT. Treatment of cognitive impairment after poststroke depression: a double-blind treatment trial. Stroke. 2000;31:1482–6.PubMedCrossRefGoogle Scholar
  121. 121.
    Hackett ML, Anderson CS, House A, Xia J. Interventions for treating depression after stroke. Cochrane Database Syst Rev. 2008; (4):CD003437.Google Scholar
  122. 122.
    Mitchell PH, Veith RC, Becker KJ, Buzaitis A, Cain KC, Fruin M, et al. Brief psychosocial-behavioral intervention with antidepressant reduces poststroke depression significantly more than usual care with antidepressant: living well with stroke: randomized, controlled trial. Stroke. 2009;40:3073–8.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Visser MM, Heijenbrok-Kal MH, Van’t Spijker A, Lannoo E, JJV B, et al. Problem-solving therapy during outpatient stroke rehabilitation improves coping and health-related quality of life. Stroke. 2016;47:135–42.PubMedCrossRefGoogle Scholar
  124. 124.
    Towfighi A, Obviagele B, El Husseini N, Hackett ML, Jorge RE, Kissela BM, et al. Poststroke depression: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017;48:e30–43.PubMedCrossRefGoogle Scholar
  125. 125.
    Meader N, Moe-Byrne T, Llewellyn A, Mitchell AJ. Screening for post- stroke major depression: a meta-analysis of diagnostic validity studies. J Neurol Neurosurg Psychiatry. 2014;85:198–206.PubMedCrossRefGoogle Scholar
  126. 126.
    Brown RF, Valpiani EM, Tennant CC, Dunn SM, Sharrock M, Hodgkinson S, et al. Longitudinal assessment of anxiety, depression, and fatigue in people with multiple sclerosis. Psychol Psychother. 2009;82(Part 1):41–56.PubMedCrossRefGoogle Scholar
  127. 127.
    Arnett PA, Higginson CI, Voss WD, Wright B, Bender WI, Wurst JM, et al. Depressed mood in multiple sclerosis: relationship to capacity-demanding memory and attentional functioning. Neuropsychology. 1999;13:434–46.PubMedCrossRefGoogle Scholar
  128. 128.
    Tarrants M, Oleen-Burkey M, Castelli-Haley J, et al. The impact of comorbid depression on adherence to therapy for multiple sclerosis. Mult Scler Int. 2011;2011:271321.PubMedPubMedCentralGoogle Scholar
  129. 129.
    Stenager EN, Stenager E, Koch-Henrikson N, Brønnum-Hansen H, Hyllested K, Jensen K, et al. Suicide and multiple sclerosis: an epidemiological investigation. J Neurol Neurosurg Psychiatry. 1992;55:542–5.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Fiest KM, Walker JR, Bernstein CN, Graff LA, Zarychanski R, Abou-Setta AM, et al. Systematic review and meta-analysis of interventions for depression and anxiety in persons with multiple sclerosis. Mult Scler Relat Disord. 2016;5:12–26.PubMedCrossRefGoogle Scholar
  131. 131.
    Feinstein A. Multiple sclerosis and depression. Mult Scler J. 2011;17(11):1276–81.CrossRefGoogle Scholar
  132. 132.
    Goldman Consensus Group. The Goldman consensus statement on depression in multiple sclerosis. Mult Scler. 2005;11:328–37.CrossRefGoogle Scholar
  133. 133.
    Honarmand K, Feinstein A. Validation of the hospital anxiety and depression scale for use with multiple sclerosis patients. Mult Scler. 2009;15:1518–24.PubMedCrossRefGoogle Scholar
  134. 134.
    Benedict RH, Fishman I, McClellan MM, Bakshi R, Weinstock-Guttman B. Validity of the Beck Depression Inventory-Fast Screen in multiple sclerosis. Mult Scler. 2003;9:393–6.PubMedCrossRefGoogle Scholar
  135. 135.
    Lowe B, Unutzer J, Callahan CM, Perkins AJ, Kroenke K. Monitoring depression treatment outcomes with the Patient Health Questionnaire-9. Med Care. 2004;42:1194–201.PubMedCrossRefGoogle Scholar
  136. 136.
    Zimmerman M, Chelminski I, McGlinchey JB, Posternak MA. A clinically useful depression outcome scale. Compr Psychiatry. 2008;49:131–40.PubMedCrossRefGoogle Scholar
  137. 137.
    Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess. 1996;67(3):588–97.PubMedCrossRefGoogle Scholar
  138. 138.
    Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression scale: an updated literature review. J Psychosom Res. 2002;52:69–77.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Zimmerman M, Martinez JH, Friedman M, Boerescu DA, Attiullah N, Toba C. How can we use depression severity to guide treatment selection when measures of depression categorize patients differently? J Clin Psychiatry. 2012;73(10):1287–91.PubMedCrossRefGoogle Scholar
  140. 140.
    Contrave® (bupropion hydrochloride; naltrexone hydrochloride; extended release oral tablet). [package insert from internet] La Jolla: Orexigen Therapeutics; 2014. [cited 9 March 2017]. Available at:
  141. 141.
    Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol. 2007;152(6):946–51.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: a review of postmarketing data. Clin Infect Dis. 2006;42:1578–83.PubMedCrossRefGoogle Scholar
  143. 143.
    Richard IH, Kurlan R, Tanner C, Factor S, Hubble J, Suchowersky O, et al. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson’s disease. Parkinson study group. Neurology. 1997;48(4):1070–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Eldepryl® (selegeline hydrochloride oral tablet). [package insert from internet]. Tampa: Somerset Pharmaceuticals; 2008. [cited 12 March 2017]. Available at:
  145. 145.
    Wilens TE, Haight BR, Horrigan JP, Hudziak JJ, Rosenthal NE, Connor DF, et al. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry. 57(7):793–801.PubMedCrossRefGoogle Scholar
  146. 146.
    American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder, 2nd. American Psychiatric Association: Washington, DC, 2010. Accessed 1/18/17 at
  147. 147.
    Honig A, Kuyper AMG, Schene AH, van Melle JP, de Jonge P, Tulner DM, et al. Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Psychosom Med. 2007;69:606–13.PubMedCrossRefGoogle Scholar
  148. 148.
    Eisenberg MJ, Grandi SM, Gervais A, O’Loughlin J, Paradis G, Rinfret S, et al. Bupropion for smoking cessation in patients hospitalized with acute myocardial infarction: a randomized, placebo-controlled trial. J Am Coll Cardiol. 2013;61:524–32.PubMedCrossRefGoogle Scholar
  149. 149.
    Grandi SM, Eisenberg MJ, Joseph L, O’Loughlin JO, Paradis G, Filion KB. Cessation treatment adherence and smoking abstinence in patients after acute myocardial infarction. Am Heart J. 2016;173:35–40.PubMedCrossRefGoogle Scholar
  150. 150.
    Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24:205–14.PubMedCrossRefGoogle Scholar
  151. 151.
    Cipriani A, La Ferla T, Furukawa TA, Signoretti A, Nakagawa A, Churchill R, et al. Sertraline versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2010;(4):CD006117.Google Scholar
  152. 152.
    Smitherman TA, Walters AB, Maizels M, Penzien DB. The use of antidepressants for headache prophylaxis. CNS Neurosci Ther. 2011;5:462–9.CrossRefGoogle Scholar
  153. 153.
    Voican CS, Corruble E, Naveau S, Perlemuter G. Antidepressant-induced liver injury: a review for clinicians. Am J Psychiatry. 2014;171:404–15.PubMedCrossRefGoogle Scholar
  154. 154.
    Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2011; CD006528.Google Scholar
  155. 155.
    Nieuwstraten CE, Dolovich LR. Bupropion versus selective serotonin-reuptake inhibitors for treatment of depression. Ann Pharmacother. 2001;35(12):1608–13.PubMedCrossRefGoogle Scholar
  156. 156.
    Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg Med J. 2001;18(4):236–41.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Marks DM, Park MH, Ham BJ, Han C, Patkar AA, Masand PS, et al. Paroxetine: safety and tolerability issues. Expert Opin Drug Saf. 2008;7(6):783–94.PubMedCrossRefGoogle Scholar
  158. 158.
    Patel K, Allen S, Haque M, Angelescu I, Baumeister D, Tracy DK. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. Ther Adv Psychopharmacol. 2016;6(2):99–144.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Gartlehner G, Gaynes B, Hansen RA, Thieda P, DeVeaugh-Geiss A, Krebs EE, et al. Comparative benefits and harms of second-generation antidepressants: background paper for the American college of physicians. Ann Int Med. 2008;149(10):734–50.PubMedCrossRefGoogle Scholar
  160. 160.
    Clayton A, Kornstein S, Prakash A, Mallinckrodt C, Wohlreich M. Changes in sexual functioning associated with duloxetine, escitalopram, and placebo in the treatment of patients with major depressive disorder. J Sex Med. 2007;4:917–29.PubMedCrossRefGoogle Scholar
  161. 161.
    Jacobsen PL, Mahableshwarkar AR, Palo WA, Chen Y, Dragheim M, Clayton AH. Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis. CNS Spect. 2016;21(5):367–78.CrossRefGoogle Scholar
  162. 162.
    Clayton AH, Kennedy SH, Edwards JB, Gallipoli S, Reed CR. The effect of vilazodone on sexual function during the treatment of major depressive disorder. J Sex Med. 2013;10(10):2465–76.PubMedCrossRefGoogle Scholar
  163. 163.
    Fetzima® (levomilnacipran extended-release oral capsule). [package insert from internet]. Irvine: Allergan USA; 2016. [cited 19 Nov 2017]. Available at:
  164. 164.
    Viibryd® (vilazodone hydrochloride oral tablet). [package insert from internet]. Irvine: Allergan USA; 2017. [cited 19 Nov 2017]. Available at:

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Leigh Jennings
    • 1
  1. 1.Department of PsychiatryMethodist Healthcare SystemsSan AntonioUSA

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