Fluvoxamine: An Antidepressant for the Elderly?

John M. Kellett Consultant Psychiatrist and Senior Lecturer, Department of Geriatric Medicine, St. George's Hospital & Medical School, London, England

Though depression remains as common in the elderly as in Efficacy younger adults, it is more frequently accompanied and precipitated by physical illness (Murphy 1983). This Although it is becoming common practice to test efficacy combined with the normal changes of aging (eg. prostatic by comparison with an antidepressant of proven strength, hypertrophy, increased intraocular pressure, constipation, there is no substitute for a placebo-controlled study. Wakelin vertebrobasilar insufficiency and ischaemic heart disease) (1986) describes such a study in severely-depressed patients render this group especially susceptible to the side effects of over the age of 59. Following a 1-week placebo washout, 33 traditional tricyclic antidepressants (cholinergic blockade patients were given fluvoxamine at a mean dose of 161 mg, [Snyder and Yamamura 1977], postural hypotension [Muller and 14 patients were provided a placebo. By the second et al 1961], and cardiac arrhythmias [Moir et al 1972]), week, double blind assessment using the Hamilton particularly when taken in overdose. Though ECT is a safe Depression Scale, and a Clinical Global Improvement Scale, and effective remedy for this age group (Baldwin and Jolley indicated significantly greater (p<0.05) improvement in the 1986; Benbow 1989; Burvill et al 1991), the newer antide- active group, which remained throughout the trial of 4 weeks. pressants are often particularly suitable for this group. Double blind comparative trials of fluvoxamine have been The clinician will have a series of questions to be performed with imipramine (Wakelin 1986), mianserin (Keet answered before being prepared to add a new antidepressant et al 1989), and dothiepin (Ashford and Rahman 1990). The to a portfolio of therapeutics. trials are summarized in Table 2.

Table 1 Comparison of fluvoxamine and placebo Hamilton & CGI scores (in parentheses) and % response at 4 weeks.

N Pre Week 1 Week 2 Week 3 Week 4 Responders

Fluvoxamine 33 24.7(4.8) 19.6(3.6) 15.6(2.8)* 12.4(2.4) 10.5(2.1)* 56.1*

Placebo 14 25.4(4.7) 22.1(3.9) 21.9(3.5) 20.4(3.5) 19.4(3.1) 21.5

* difference from placebo significant at p

Address reprint requests to: Dr. J.M. Kellett, St. George's Hospital Medical School, Cranmer Terrace, Tooting, London, SW17 ORE England

J Psychiatr Neurosci, VoL 16, No. 2 (SuppL 1), 1991 July 1991 Fluvoxamine: An Antidepressantfor the Elderly? Z7

Table 2 Double blind comparative trials of fluvoxamine.

Author Wakelin(1986) Keet et al(1989) Ashford and Rahman(1990)

Fluvoxamine Imipramine Fluvoxamine Mianserin Fluvoxamine Dothiepin

Number entered: 33 29 25 25 26 26 Number completed: 24 17 16 15 17 19 Ages (mean) 60-71(65) 60-70(66) (75.7) (76.7) 65-86(73) 61-85(75) Male Sex 9 6 10 6 6 6 Placebo washout: 1 week 1 week 1 week Mean dose 161mg 160mg 175mg 66mg Measures HAMD (CGI) MADRS (CGI) MADRS (CGI) Minimum Score 15 30 30 Score on entry 24.7 25.2 36 36 36 36 at week 1 19.6(3.6) 21.4(3.6) 31(3.4) 30(3.2) 29(3.6) 29(3.6) at week 2 15.6(2.8) 17.5(3.1) 28(2.8) 29(3.4) 25(3.2) 26(3.3) at week 3 12.4(2.4) 13.8(2.5) at week 4 10.5(2.1) 11.5(2.1) 25(2.7) 24(2.9) 15(2.2) 18(2.6) at week 5 23(2.8) 20(2.7) 13(1.8) 14(2.3)

Although there are slight differences, such as the speed In a large, open study of 135 patients aged over 64, with with which the CGI (Clinical Global Improvement - lower a DSM III major depression and a MADRS score of at scores are better) became significantly different from the least 25, Houillon and Douge (1989) attempted to separate control and imipramine groups (week 3 for imipramine vs. the effects of fluvoxamine on individual symptom clusters. week 2 for fluvoxamine), and the fluvoxamine group shows Both the MADRS and the Tyrer scale for anxiety showed significantly greater improvement at week 2 compared to significant improvement in the first week, though the mianserin, a reasonable view is that these drugs are of antidepressant effect was more marked in the second week. comparable efficacy, with the possibility that fluvoxamine Apparent sadness, expressed sadness, tension, reduction of works more quickly. In the Wakelin study, by dividing the sleep, difficulty with concentration, attitude, inability to Hamilton scale into 6 factors there was a suggestion that feel, suicidal ideation, internal tension, unjustified anxiety, fluvoxamine acted more quickly on retardation, anxiety, and and muscular tension were significantly improved by day somatisation than imipramine. 7, while a reduction in pessimistic thoughts, hypochondri- Table 3 Percentage of patients with side effects (studies with older patients). Drug Fluvoxamine Dothiepin Mianserin Imipramine Placebo Author Tebbs & Houillon & Ahford & Keet Ashford & Keet Martin+ Douge+ Rahman et al Wakelin Rahman et al Wakelin Wakelin Number of patients 1096 133 26 25 32 26 25 29 14 Side Effect Nausea 15 13 23 0 41 12 12 10 20 Vomiting 5 8 0 4 - 0 4 - - Constipation <1 5 8 0 25 8 4 21 7 Dry mouth 3 6 4 - 25 15 - 52 21 Dizziness 7 6 19 12 9 15 8 24 0 Confusion <1 - - 4 - - 4 14 0 Asthenia 4 12* 4 0 - 12 4 - - Somnolence 4 - 8 8 16 8 16 25 17 * fatique; + open trial 28 Journal ofPsychiatry & Neuroscience Supplement I Vol. 16, No. 2,1l99

Table 4 Effects on the autonomic system. Fluvoxamine Amitryptilene Doxepin

Salivary flow - 0.1 - 0.8 - 0.75** (differences from placebo in g./2 minutes) Pupil diameter + 0.25 - 0.75** - 0.6** (differences from placebo in mm.) Pulse rate standing - 3.5 + 4.2 + 4.7 (differences from placebo in beats/min) Systolic blood pressure standing + 3.3 - 0.5 - 9.4* (differences from placebo in mm. Hg.) Diastolic blood pressure standing - 0.3 - 0.8 - 4.5* (differences from placebo in mm. Hg.)

* pamitriptyline and doxepin on the autonomic systems of 17 healthy, young volunteers, in maximum doses of 100 mg, CONCLUSIONS 75 mg and 75 mg respectively, at 3 hours. The authors concluded that fluvoxamine has little effect Despite sharing the side effects of all the 5HT specific on the autonomic system versus the comparison drugs, drugs of nausea, and occasional vomiting (side effects which though the ability of doxepin and amitryptilene to constrict diminish over a week or two), fluvoxamine is likely to prove the pupil, rendered elucidation difficult. a valuable antidepressant for the elderly. Its relatively short More serious from the point of view of overdose is the half life makes its use easier to regulate than fluoxetine, effect on the heart. Prager et al (1986) examined the effect which is also more likely to excite epilepsy. Bearing in mind July 1991 Fluvoxamine: An Antidepressantfor the Elderly? 29

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