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Meta-Analysis
. 2006 Jan 25;2006(1):CD003491.
doi: 10.1002/14651858.CD003491.pub2.

Antidepressants for depressed elderly

P Mottram  1 , K Wilson, J Strobl
Affiliations
Meta-Analysis

Antidepressants for depressed elderly

P Mottram et al. Cochrane Database Syst Rev. .

Abstract

Background: Depression is a relatively common experience in older adults. The syndrome is associated with considerable distress, morbidity and service commitment. Approximately two thirds of patients presenting with severe forms will respond to antidepressant treatment and the last twenty years has witnessed a great increase in the number of these drugs. Older, frail people are particularly vulnerable to side effects.

Objectives: The aims of this review were to examine the efficacy of antidepressant classes, to compare the withdrawal rates associated with each class and describe the side effect profile of antidepressant drugs for treating depression in patients described as elderly, geriatric, senile or older adults, aged 55 or over.

Search strategy: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies) was searched (2003-08-13). Reference lists of relevant papers and previous systematic reviews were hand searched for published reports and citations of unpublished studies.

Selection criteria: Only randomised controlled trials were included. Trials had to compare at least two active antidepressant drugs in the treatment of depression.

Data collection and analysis: Reviewers extracted data independently. In examining efficacy, the reviewers assumed that people who died or dropped out had no improvement. Withdrawal rates irrespective of cause and specifically due to side effects were compared between drug classes. Relative risk (RR) for dichotomous data and weighted mean difference for continuous data were calculated with 95% confidence intervals (CI). Qualitative side effect data were reported in terms of ratios of side effects and percentage of patients experiencing specific side effects.

Main results: A total of 29 trials provided data for inclusion in the review. We were unable to find any differences in efficacy when comparing classes of antidepressants. However, as the trials contained relatively small numbers of patients, these findings may be explained by a type two error. Tricyclic antidepressants (TCAs) compared less favourably with selective serotonin reuptake inhibitors (SSRIs) in terms of numbers of patients withdrawn irrespective of reason (RR: 1.24, CI 1.04, 1.47) and number withdrawn due to side effects (RR: 1.30, CI 1.02, 1.64). Subgroup analyses demonstrated that TCA related antidepressants had similar withdrawal rates to SSRIs irrespective of reason of withdrawal (RR: 1.49, CI 0.74, 2.98) or withdrawal due to side effects (RR: 1.07, CI 0.43, 2.70). The qualitative analysis of side effects showed a small increased profile of gastro-intestinal and neuropsychiatric side effects associated with classical TCAs.

Authors' conclusions: Our findings suggest that SSRIs and TCAs are of the same efficacy. However, we have found some evidence suggesting that TCA related antidepressants and classical TCAs may have different side effect profiles and are associated with differing withdrawal rates when compared with SSRIs. The review suggests that classical TCAs are associated with a higher withdrawal rate due to side effect experience, although these results must be interpreted with caution due to the relatively small size of the review and the heterogeneity of the drugs and patient populations.

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Conflict of interest statement

None

Figures

1.1
1.1. Analysis
Comparison 1 All TCAs versus SSRIs, Outcome 1 Failed to recover.
1.2
1.2. Analysis
Comparison 1 All TCAs versus SSRIs, Outcome 2 Depression severity (HAM‐D Scale).
1.3
1.3. Analysis
Comparison 1 All TCAs versus SSRIs, Outcome 3 Withdrawal due to side‐effects.
1.4
1.4. Analysis
Comparison 1 All TCAs versus SSRIs, Outcome 4 Total withdrawal rates.
2.1
2.1. Analysis
Comparison 2 All TCAs versus MAOIs, Outcome 1 Failed to recover.
2.3
2.3. Analysis
Comparison 2 All TCAs versus MAOIs, Outcome 3 Withdrawal due to side effects.
2.4
2.4. Analysis
Comparison 2 All TCAs versus MAOIs, Outcome 4 Total withdrawal rates.
3.1
3.1. Analysis
Comparison 3 All TCAs versus Atypicals, Outcome 1 Failed to recover.
3.2
3.2. Analysis
Comparison 3 All TCAs versus Atypicals, Outcome 2 Depression severity (HAM‐D Scale).
3.3
3.3. Analysis
Comparison 3 All TCAs versus Atypicals, Outcome 3 Withdrawal due to side effects.
3.4
3.4. Analysis
Comparison 3 All TCAs versus Atypicals, Outcome 4 Total withdrawal rates.
4.1
4.1. Analysis
Comparison 4 SSRIs versus MAOIs, Outcome 1 Failed to recover.
4.3
4.3. Analysis
Comparison 4 SSRIs versus MAOIs, Outcome 3 Withdrawal due to side effects.
4.4
4.4. Analysis
Comparison 4 SSRIs versus MAOIs, Outcome 4 Total withdrawal rates.
5.1
5.1. Analysis
Comparison 5 Classical TCAs versus SSRIs, Outcome 1 Failed to recover.
5.2
5.2. Analysis
Comparison 5 Classical TCAs versus SSRIs, Outcome 2 Depression severity (HAM‐D Scale).
5.3
5.3. Analysis
Comparison 5 Classical TCAs versus SSRIs, Outcome 3 Withdrawal due to side effects.
5.4
5.4. Analysis
Comparison 5 Classical TCAs versus SSRIs, Outcome 4 Total withdrawal rates.
6.1
6.1. Analysis
Comparison 6 Related TCAs versus SSRIs, Outcome 1 Failed to recover.
6.2
6.2. Analysis
Comparison 6 Related TCAs versus SSRIs, Outcome 2 Depression severity (HAM‐D Scale).
6.3
6.3. Analysis
Comparison 6 Related TCAs versus SSRIs, Outcome 3 Withdrawal due to side effects.
6.4
6.4. Analysis
Comparison 6 Related TCAs versus SSRIs, Outcome 4 Total withdrawal rates.
7.1
7.1. Analysis
Comparison 7 Classical TCAs versus Atypicals, Outcome 1 Failed to recover.
7.2
7.2. Analysis
Comparison 7 Classical TCAs versus Atypicals, Outcome 2 Depression severity (HAM‐D Scale).
7.3
7.3. Analysis
Comparison 7 Classical TCAs versus Atypicals, Outcome 3 Withdrawal due to side effects.
7.4
7.4. Analysis
Comparison 7 Classical TCAs versus Atypicals, Outcome 4 Total withdrawal rates.
8.1
8.1. Analysis
Comparison 8 Related TCAs versus Atypicals, Outcome 1 Failed to recover.
8.2
8.2. Analysis
Comparison 8 Related TCAs versus Atypicals, Outcome 2 Withdrawal due to side effects.
8.3
8.3. Analysis
Comparison 8 Related TCAs versus Atypicals, Outcome 3 Total withdrawal rates.
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Update of

  • doi: 10.1002/14651858.CD003491

References

References to studies included in this review

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Goldstein 1982 {published data only}
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Harding 1973 {published data only}
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Hebenstreit 1988 {published data only}
    1. Baumhackl U, Biziere K, Fischbach R, Geretsegger C, Hebenstreit G, Radmayr E, et al. Efficacy and tolerability of moclobemide compared with imipramine in depressive disorder (DSM‐III): an Austrian double‐blind, multicentre study. British Journal of Psychiatry 1989;155 Supp 6:78‐83. - PubMed
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Hell 1994 {published data only}
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Hostmaelingen 1989 {published data only}
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Jarvik 1982 {published data only}
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Jessel 1981 {published data only}
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Kane 1983 {published data only}
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Karlsson 2000 {published data only}
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Katona 1999b {published data only}
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Katona 1998 {published data only}
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Kerr 1984a {published data only}
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Khan 1981 {published data only}
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Kivella 1987 {published data only}
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Koncevoj 1989 {published data only}
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Koran 1995 {published data only}
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Laghrissie‐Thode '95 {published data only}
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Lapierre 1991 {published data only}
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Lauritzen 1994 {published data only}
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Lauritzen 1996a {published data only}
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Lauritzen 1996b {published data only}
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Lipsedge 1971 {published data only}
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Malsch 1996 {published data only}
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Mamo 2000 {published data only}
    1. Mamo DC, Sweet RA, Mulsant BH, Pollock BG, Miller MD, Stack JA, et al. Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: a prospective double‐blind study in depressed elderly patients. Americal Journal of Geriatric Psychiatry 2000;8(3):226‐31. - PubMed
Marais 1974 {published data only}
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McEntee 1996 {published data only}
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Meignan‐Debray 1990 {published data only}
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Meredith 1994 {published data only}
    1. Meredith CH, Feighner JP, Hendrickson G. A double blind comparative evaluation of the efficacy and safety of Nomifensine, Impiramine and placebo in depressed geriatric outpatients. Journal of Clinical Psychiatry 1984;45(4 Sec 2):73‐77. - PubMed
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Moller 1993 {published data only}
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Moller 2000 {published data only}
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Montgomery 1981 {published data only}
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Montgomery 1983 {published data only}
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Nair 1993 {published data only}
    1. Nair NPV, Amin M, Holm P, Katona C, Klitgaard N, Ng Ying Kin NM, et al. Moclebemide and nortriptyline in elderly depressed patients A randomised multicentre trial against placebo. Journal of Affective Disorders 1995;33:1‐9. - PubMed
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Newhouse 1988 {published data only}
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Newhouse 1996 {published data only}
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Pancheri 1994 {published data only}
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Poldinger 1982b {published data only}
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Pollock 1998 {published data only}
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Rickels 1994c {published data only}
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Robertson 1994 {published data only}
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Robinson 2000 {published data only}
    1. Robinson RG, Schultz SK, Castillo C, Kopel T, Kosier JT, Newman RM, et al. Nortriptyline versus fluoxetine in the treatment of depression and in short‐term recovery after stroke: a placebo‐controlled, double‐blind study. American Journal of Psychiatry 2000;157(3):351‐9. - PubMed
Roose 1987 {published data only}
    1. Roose SP, Glassman AH, Giardina EG, Johnson LL, Walsh BT, Bigger JT Jr. Cardiovascular effects of imipramine and bupropion in depressed patients with congestive heart failure. Journal of Clinical Psychopharmacology 1987;7(4):247‐51. - PubMed
Roose 1994 {published data only}
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Roose 1998 {published data only}
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Rothblum 1982 {published data only}
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Sacchetti 1997 {published data only}
    1. Sacchetti E, Conte G, Guarneri L, Calzeroni A, Bertini M, Panariello A. Effectiveness of fluvoxamine and paroxetine in major depressives with psychotic features. Human Psychopharmacology 1997;12:277‐8.
Scarzella 1985 {published data only}
    1. Scarzella L, Scarzella R, Mailland F, Bergamasco B. Amineptine in the management of the depressive syndromes.. Progresses in Neuro‐Psychopharmachology and Biological Psychiatry 1985;9(4):429‐39. - PubMed
Schatzberg 2000 {published data only}
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Schifano 1990 {published data only}
    1. Schifano F, Garbin A, Renesto V, Dominicis MG, Trinciarelli G, Silvestri A, et al. A double blind comparison of mianserin and maprotiline in depressed medically ill elderly people. Acta Psychiatrica Scandinavica 1990;81:289‐94. - PubMed
Schiwy 1989a {published data only}
    1. Schiwy W, Heath WR, Delini Stula A. Therapeutic and side‐effect profile of a selective and reversible MAO‐A inhibitor, brofaromine Results of dose‐finding trials in depressed patients. Journal of Neural Transmission. Supplementum 1989;28:33‐44. - PubMed
Schiwy 1989b {published data only}
    1. Schiwy W, Heath WR, Delini Stula A. Therapeutic and side‐effect profile of a selective and reversible MAO‐A inhibitor, brofaromine Results of dose‐finding trials in depressed patients. Journal of Neural Transmission. Supplementum 1989;28:33‐44. - PubMed
Schneider 1998a {published data only}
    1. Schneider LS, Small GW, Clary CM. Estrogen replacement therapy status and antidepressant to sertraline. 151st Annual Meeting of the American Psychiatric Association. Toronto, Ontario, Canada. 30th May 4th June. 1998.
Schneider 1998b {published data only}
    1. Schneider L, Small G, Clary C. Does estrogen replacement therapy augment response to sertraline in depressed elderly women. XXIst Collegium Internationale Neuro Psychopharmacologicum, Glasgow, Scotland. 12th 16th July. 1998.
Schone 1994 {published data only}
    1. Geretsegger C, Bohmer F, Ludwig M. Paroxetine in the elderly depressed patient:randomized comparison with Fluoxetine of effeicacy,cognitive and behavioural effects. International Clinical Psychopharmacology 1994;9:25‐9. - PubMed
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Stanley 1998 {published data only}
    1. Stanley N, Kimber S, Fairweather DB, Hindmarch I. Venlafaxine and dothiepin in depressed elderly patients: A comparison of efficacy and effects on cognition. 11th European College of Neuropsychopharmacology Congress. Paris, France. 31st October 4th November 1998. 1998:P.1.044.
Stewart 1968 {published data only}
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Stoppe 1998 {published data only}
    1. Stoppe A, Forlenza OV, Hirata E, Ferreira RC, Almeida OP. Antidepressant Efficacy and Tolerability Comparison of Sertraline and Imipramine in Brazilian Elderly Outpatients. 151st Annual Meeting of the American Psychiatric Association. Toronto, Ontario, Canada. 30th May 4th June. 1998.
Strik 1998 {published data only}
    1. Strik J, Honig A, Lousberg R, Cheriex EC, van‐Praag HM. Cardiac side effects of two SSRI's in middle‐aged and elderly depressed patients. XXIst Collegium Internationale Neuro psychopharmacologicum, Glasgow, Scotland. 12th 16th July. 1998.
    1. Strik JJ, Honig A, Lousberg R, Cheriex EC, Praag HM. Cardiac side‐effects of two selective serotonin reuptake inhibitors in middle‐aged and elderly depressed patients. International Clinical Psychopharmacology 1998;13(6):263‐7. - PubMed
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Taragano 1997 {published data only}
    1. Taragano FE, Lyketsos CG, Mangone CA, Allegri RF, Comesana‐Diaz E. A double‐blind, randomized, fixed‐dose trial of fluoxetine vs amitriptyline in the treatment of major depression complicating Alzheimer's disease. Psychosomatics 1997;38(3):246‐52. - PubMed
Thayssen 1981 {published data only}
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Tourigny‐Rivard 1996 {published data only}
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Volz 1995 {published data only}
    1. Volz H P, Muller H, Moller H J. Are there any differences in the safety and efficacy of brofaromine and imipramine between non‐elderly and elderly patients with major depression?. Neuropsychobiology 1995;32(1):23‐30. - PubMed
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    1. Volz HP, Gleiter CH, Moller HJ. Brofaromine versus imipramine in in‐patients with major depression‐‐a controlled trial. Journal of Affective Disorders 1997;44(2‐3):91‐9. - PubMed
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Wakelin 1986 {published data only}
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    1. Weber E, Stack J, Pollock BG, Mulsant B, Begley A, Mazumdar S ET AL. Weight change in older depressed patients during acute pharmacotherapy with paroxetine and nortriptyline: a double‐blind randomized trial. American Journal of Geriatric Psychiatry 2000;8(3):245‐50. - PubMed
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References to studies awaiting assessment

Branconnier 1981 {published data only}
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