Mohammed T. Abou-Saleh

PHARMACOLOGICAL TREATMENT OF DEPRESSION 441It has also been related to cognitive impairment, physical andpsychiatric co-morbidity, late onset and presence of melancholicand psychotic features 41 . Moreover, elderly patients with anxiousdepression are less responsive to nortriptyline than are thosewithout significant anxiety symptoms 42 .Although TCAs 16 and MAOIs 43 have shown efficacy, the SSRIsare specifically advocated 41 . Fluvoxamine has shown efficacy(70% good response) in desipramine non-responders 44,45 , andpatients who were intolerant of fluoxetine completed a trial ofsertraline with a response rate of 76% 46 . Efficacy has also beenshown for trazodone 47 , bupropion 48 and venlafaxine 49 . Combinationand augmentation strategies have been advocated 41 . Lithiumaugmentation in TCA non-responders is effective in 20–65% ofcases 50–52 . It is, however, conducive to cognitive and neurologicalside effects in 50% of patients 50,51,53,54 . Lithium has been successfullyadded to SSRIs, notwithstanding the risk of neurotoxicitywith an SSRI–lithium combination 41 . Advocated augmentation/combination strategies includes TCA/triodo-thyronine; SSRI/TCA; SSRI/anticonvulsants; and SSRI/oestrogen 41 , and elderlypatients requiring adjunctive medication to achieve remission mayneed continuation of adjunctive medication to remain well and toavoid early relapse 55 .For refractory bipolar disorders, a recent review 56 concludedthat the safest combination of mood stabilizers is valproate pluslithium. This was also shown in a series of elderly patients withlithium-resistant rapid cycling mania 57 .CONCLUSIONAlthough there have been impressive advances in the pharmacologicaltreatment of mood disorders in general, there has been arelative paucity of controlled studies in the elderly, particularly inmaintenance and prophylaxis. Generalization from the results ofstudies of younger patients may be inappropriate in view of thesignificant changes associated with normal ageing and concomitantmedical illness, which affect the pharmacokinetics andpharmacodynamics of psychotropic drugs.Nevertheless, there has been a change of culture. The nihilismthat had prevailed in the treatment of mood disorders in late lifehas been replaced by cautious optimism with regard to the resultsof controlled trials in naturalistic settings, as well as studies inhigh-risk groups, including patients with multiple medicalconditions and subsyndromal states.A large majority of elderly patients with depression could betreated successfully with antidepressants, particularly the SSRIs,because of their favourable side-effect profiles and their lowtoxicity in overdose. The SSRIs, however, challenge the clinicianwith their clinically significant drug–drug interactions. Patientswho improve should receive continuation of prophylactic treatmentwith the same dose. For mania, lithium remains the optimaltreatment, with anticonvulsants, particularly divaloproex, providinga second-line treatment. The efficacy and safety of atypicalneuroleptics remain to be evaluated in both acute and long-termmanagement of bipolar illness. There is also hope for those withresistant-mood disorders with the design of augmentation/combination strategies, which require further evaluation.REFERENCES1. Bland RC. Epidemiology of affective disorders: a review. Can JPsychiat 1997; 42: 367–77.2. Dew MA, Reynolds CF III, Houck PR et al. Temporal profiles of thecourse of depression during treatment. Arch Gen Psychiat 1997; 54:1016–24.3. Lebowitz BD, Pearson JL, Schneider LS et al. Diagnosis andtreatment of depression in late life: consensus statement update. JAm Med Assoc 1997; 278: 1186–90.4. Salzman C, DuRand C. Pharmacological treatment of depression. InCopeland JRM, Abou-Saleh MT, Blazer D, eds, Principles andPractice of Geriatric Psychiatry 1st edn. Chichester: Wiley, 1994: 575–80.5. Catterson ML, Preskorn SH, Martin RM. Pharmacodynamic andpharmacokinetic considerations in geriatric psychopharmacology.Geriat Psychiat 1997; 20: 205–19.6. Hermann N, Bremner EK, Naranjo CA. Pharmacotherapy of late lifemood disorders. Clin Neurosci 1997; 4: 41–7.7. Rivard MFT. Pharmacotherapy of affective disorders in old age. CanJ Psychiat 1997; 42(suppl 1): 10–18S.8. Salzman C, Schneider L, Alexopoulos G. Pharmacological treatmentof depression in late life. In Bloom F, Kupfer D, eds, Psychopharmacology:the Fourth General of Progress. New York: Raven,1995; 1771–7.9. Robinson RG, Morris PH, Fedoroff JP. Depression and cerebrovasculardisease. J Clin Psychiat 1990; 51: 26–33.10. Georgotas A, McCue RE, Hapworth W et al. Comparative efficacyand safety of MAOI vs. TCAs in treating depression in the elderly.Biol Psychiat 1986; 21: 1155–66.11. Lazarus LW, Groves L, Gierl B et al. Efficacy of phenelzine ingeriatric depression. Biol Psychiat 1986; 21: 699–701.12. Pancheri P, Delle CR, Donnini M et al. Effects of moclobemide ondepressive symptoms and cognitive performance in a geriatricpopulation: a controlled comparative study vs. imipramine. ClinNeuropharmacol 1994; 17(suppl 1): 58S–73S.13. Nair NP, Amin M, Holm P et al. Moclobemide and nortriptyline inelderly depressed patients: a randomised multicentre trial againstplacebo. J Affect Disord 1995; 33: 1–9.14. Roth M, Mountjoy CQ, Amrein R. The International CollaborativeStudy Group. Moclobemide placebo-controlled trial. Br J Psychiat1996; 16: 149–57.15. Tollefson GD, Holman SL. Analysis of the Hamilton DepressionRating Scale factors from a double-blind, placebo-controlled trial offluoxetine in geriatric major depression. Int Clin Psychopharmacol1993; 8: 253–9.16. Roose SP, Glassman AH, Attia E, Woodring S. Comparative efficacyof selective serotonin reuptake inhibitors and tricyclics in thetreatment of melancholia. Am J Psychiat 1994; 151: 1735–9.17. Mittmann N, Shear NH, Busto VE et al. Comparative evaluation ofthe efficacy and safety of tricyclic antidepressants and serotoninreuptake inhibitors in the elderly: a meta-analysis. Clin Invest Med1994; 18: B53.18. Spigset O, Hedenmalm K. Hyponatremia in relation to treatmentwith antidepressants: a survey of reports in the World HealthOrganization database for spontaneous reporting of adverse drugreactions. Pharmacotherapy 1997; 17: 348–52.19. Nemeroff CB, DeVane CL, Pollock BG. Newer antidepressants andthe cytochrome P450 system. Am J Psychiat 1996; 153: 311–20.20. Preskorn SH. Reducing the risk of drug–drug interactions: a goal ofrational drug development. J Clin Psychiat 1996; 57(suppl 1): 3–6S.21. Solai LK, Mulsant BH, Pollock BG et al. Effect of sertraline onplasma nortriptyline levels in depressed elderly. J Clin Psychiat 1997;58: 440–43.22. Volz HP, Moller HJ. Antidepressant drug therapy in the elderly: acritical review of controlled clinical trials conducted since 1980.Pharmacopsychiatry 1994; 27: 93–100.23. Mahapatra SN, Hackett D. A randomised double-blind, parallelgroupcomparison of venlafaxine and dothiepin in geriatric patientswith major depression. Int J Clin Pract 1997; 51: 209–13.24. Fontaine R, Ontiveros A, Elie R et al. A double-blind comparison ofnefazodone, imipramine and placebo in major depression. J ClinPsychiat 1994; 55: 234–41.25. Murphy E. The prognosis of depression and response to antidepressivetherapies. Br J Psychiat 1983; 142: 111–19.26. Abou-Saleh MT, Coppen A. Classification of depression andresponse to anti-depressive therapies. Br J Psychiat 1983; 143: 601–3.27. Stoudemire A. Recurrence and relapse in geriatric depression: areview of risk factors and prophylactic treatment strategies. JNeuropsychiat 1997; 9: 209–21.