Mohammed T. Abou-Saleh

442 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRY28. Reynolds CF. Treatment of depression in late life. Am J Med 1994;97(suppl 6A): 39–46S.29. Reynolds CF III, Frank E, Houck PR et al. Which elderly patientswith remitted depression remain well with continued interpersonalpsychotherapy after discontinuation of antidepressant medication?Am J Psychiat 1997; 154: 958–62.30. Reynolds CF III, Buysse DJ, Brunner DP et al. Maintenancenortriptyline effects on electroencephalographic sleep in elderlypatients with recurrent major depression: double-blind, placeboandplasma level-controlled evaluation. Soc Biol Psychiat 1997; 42:560–67.31. Flint AJ, Rifat SL. The effect of treatment on the two-year course oflate-life depression. Br J Psychiat 1997; 170: 268–72.32. Reynolds CF, Frank E, Perel J et al. Maintenance therapies for latelife recurrent major depression: research and review circa 1995. IntPsychogeriat 1995; 7(suppl): 27–40.33. Coppen A, Abou-Saleh MT. Lithium therapy: from clinical trials topractical management. Acta Psychiat Scand 1988; 78: 759–62.34. Abou-Saleh MT. Long-term management of affective disorder. InCopeland JRM, Abou-Saleh MT, Blazer DG, eds, Principles andPractice of Geriatric Psychiatry 1st edn. Chichester: Wiley, 1994; 587–96.35. Coppen A. Depression as a lethal disease: prevention strategies. J ClinPsychiat 1994; 55(suppl): 37–45.36. Wilson KCM, Scott M, Abou-Saleh MT et al. Long-term effects ofcognitive–behavioural therapy and lithium therapy on depression inthe elderly. Br J Psychiat 1995; 167: 653–8.37. Young RC. Bipolar mood disorders in the elderly. Geriat Psychiat1997; 20: 121–36.38. Kusumakar V, Yatham LN, Haslam DRS et al. Treatment of mania,mixed state, and rapid cycling. Can J Psychiat 1997; 42(suppl 2): 79–86S.39. Yatham LN, Kusumakar V, Parikh SV et al. Bipolar depression:treatment options. Can J Psychiat 1997; 42(suppl 2): 87–91S.40. Goff DC, Jenike MA. Treatment-resistant depression in the elderly. JAm Geriat Soc 1986; 34: 63–70.41. Kamholz BA, Mellow AM. Management of treatment resistance inthe depressed geriatric patient. Psychiat Clin N Am 1997; 19: 269–87.42. Flint AJ, Rifat SL. Anxious depression in elderly patients. Responseto antidepressant treatment. Am J Geriat Psychiat 1997; 5: 107–15.43. Georgotas A, Friedman E, McCarthy M et al. Resistant geriatricdepressions and therapeutic response to monoamine oxidaseinhibitors. Biol Psychiat 1983; 18: 195–205.44. Delgado PL, Price LH, Charney DS, Heninger GR. Efficacy offluvoxamine in treatment-refractory depression. J Affect Disord 1988;15: 55–60.45. White K, Wykoff W, Tynes LL et al. Fluvoxamine in the treatment oftricyclic resistant depression. Psychiat J Univ Ottawa 1990; 15: 156–8.46. Brown WA, Harrison W. Are patients who are intolerant to one SSRIintolerant to another? Psychopharmacol Bull 1992; 28: 253–6.47. Cole JO, Schatzberg AF, Sniffin C et al. Trazodone in treatmentresistantdepression: an open study. J Clin Psychopharmacol 1981;1(suppl): 49–54.48. Ferguson J, Cunningham L, Meredith C et al. Bupropion in tricyclicantidepressant non-responders with unipolar major depressivedisorder. Ann Clin Psychiat 1994; 6: 153–60.49. Nierenberg AA, Feighner JP, Rudolph R et al. Venlafaxine fortreatment-resistant unipolar depression. J Clin Psychopharmacol1994; 14: 419–23.50. Finch EJL, Katona CIE. Lithium augmentation in the treatment ofrefractory depression in old age. Int J Geriat Psychiat 1989; 4: 41–6.51. Flint AJ. Recent developments in geriatric psychopharmacotherapy.Can J Psychiat 1994; 39(suppl 1): S9–S18.52. Zimmer B, Rosen J, Thornton JE et al. Adjunctive lithium carbonatein nortriptyline-resistant elderly depressed patients. J Clin Psychopharmacol1991; 11: 254–6.53. Flint AJ, Rifat SL. A prospective study of lithium augmentation inantidepressant-resistant geriatric depression. J Clin Psychopharmacol1994; 14: 353–6.54. Lafferman J, Solomon K, Ruskin P. Lithium augmentation fortreatment-resistant depression in the elderly. J Geriat Psychiat Neurol1998; 1: 49–52.55. Reynolds CF III, Frank E, Perel JM et al. High relapse rate afterdiscontinuation of adjunctive medication for elderly patients withrecurrent major depression. Am J Psychiat 1996; 153: 1418–22.56. Freeman MP, Stott AL. Mood stabiliser combinations: a review ofsafety and efficacy. Am J Psychiat 1998; 155: 12–21.57. Schneider AL, Wilcox CS. Divalproate augmentation in lithiumresistantrapid cycling mania in four geriatric patients. J Affect Disord1998; 47: 201–5.Treatment-resistant DepressionAlastair J. FlintToronto General Hospital, Toronto, Ontario, CanadaTreatment resistance is a common clinical problem, reported in upto one-third of older depressed patients 1 . Many patients labelledas ‘‘treatment-resistant’’ in fact have not had an adequate courseof treatment 2 . Therefore, the first step in achieving remission ofdepressive symptoms is to ensure that the patient has been given,and has complied with, an optimum dose of antidepressant for asufficient length of time (at least 6 weeks). In treatment-resistantdepression, it is also important to investigate the patient forunidentified physical conditions (such as hypothyroidism, vitaminB 12 or folate deficiency, or hypercalcemia) that could be contributingto poor antidepressant response 2 .In patients who have failed to respond to an adequate trial ofantidepressant medication, the following options can be considered:(a) augment the antidepressant with another drug that is notprimarily an antidepressant, such as lithium, triiodothyronine,methylphenidate, pindolol, buspirone or valproate; (b) add asecond antidepressant to the first (combination therapy), e.g. adda tricyclic antidepressant (TCA) or bupropion to a selectiveserotonin-reuptake inhibitor (SSRI); (c) switch to a differentantidepressant medication; or (d) switch to electroconvulsivetherapy (ECT). The advantage of augmentation or combinationtherapy is that they do not require discontinuation of the originalantidepressant and, therefore, patients who have partiallyresponded to treatment are not put at risk of returning to theirbaseline severity of depression. Also, response may at times befaster with augmentation/combination than with a new trial ofantidepressant medication. The disadvantage of these strategies,especially in older people, is that the combination of medicationsincreases the risk of side effects and drug–drug interactions. Also,there have been no placebo-controlled trials of augmentation orcombination therapy in elderly depressed patients and so theirefficacy has not yet been established in this population 2,3 .There are virtually no research data on switching from oneantidepressant medication to another in refractory geriatric