Ó
2000 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2000 Volume 4 Pages 123 ± 125
123
Selegiline-citalopram combination in patients with Parkinson’s disease and major depression ZOLTAÂN RIHMER1 , MAÂRIA SAÂTORI 2 AND PEÂTER PESTALITY1 Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Adelaide on 11/13/14 For personal use only.
1
National Institute for Psychiatry and Neurology, and 2 Szent RoÂkus Hospital, Budapest, Hungary
Correspondence Address Dr. ZoltaÂn Rihmer, Budapest 27, POB 1, 1281 Hungary Tel/Fax: +36 1 391 53 53
Received 1 April 1999; revised 16 June 1999; accepted for publication 9 July 1999
INTRODUCTION:
We evaluated the efficacy and safety of the selegilinecitalopram combination in the treatment of major depression in patients with Parkinson’s disease. METHOD : Eight consecutive depressed outpatient s who had received previously selegiline monotherapy or (one patient) selegiline-levod opa combination (the dose of selegiline was 5-10 mg/day in each case) for mild to severe Parkinson’s disease were treated with 20 mg citalopram/day. The severity of depression was evaluated on the Hamilton Depression Rating Scale before and 8 weeks after citalopram treatment. RESULTS: The majority of the patients (six) responded well to citalopram treatment and no adverse events occurred. CONCLUSION : The combination of a low dose of selegiline (5-10 mg daily) and citalopram (20 mg daily) may be an effective and safe method in the treatment of major depression in patients with Parkinson’s disease. (Int J Psych Clin Pract 2000; 4: 123 ± 125) Keywords citalopram Parkinson’s disease combination therapy
INTRODUCTION
F
orty percent of patients with Parkinson’ s disease have clinical depression : a complication which results in a worse outcome and makes the treatment more difficult .1 Because of its favourable side-effect profile and low behavioural toxicity, the serotonin selective re-uptake inhibitor antidepressan ts (SSRIs) are promising drugs in the treatment of depression with Parkinson’ s disease.2 ,3 These patients are often on selegilin e (a selective MAO-B inhibitor) therapy because of their movement disorder. However, several review articles declare that one of the most potentially serious adverse interactions that can occur with the co-administra tion of SSRIs and MAOIs is the serious, even fatal, serotonin syndrome.4 ± 6 This is primarily true for the nonselective MAOIs such as phenelzine and tranylcypromi ne,7 ,8 and for the selective MAO-A inhibitor moclobemide.9 Selegiline is a selective MAO-B inhibitor, when given in low doses of 5 ± 20 mg/ day, and this increases the turnover of dopamine, but not of the serotonin and noradrenali ne level. However, in higher doses (30 mg/day or above), selegilin e loses its MAO-B selectivity and acts as a nonselective MAOI, inhibiting the degradation not only of dopamine, but also of serotonin and noradrenalin e,1 0 ,1 1 and in combination
depression selegiline
with SSRIs can cause serotonin syndrome .1 2 We report here the effectivenes s and safety of an SSRI-selegilin e combination for major depression in eight outpatients whose Parkinson’ s disease was previously treated with a low dose of selegilin e and who were still on selegilin e during the SSRI treatment.
PATIENTS AND METHODS Eight consecutive outpatients (all caucasians , 6M, 2F) aged between 61 and 84 years (mean 74.1), whose mild to moderate Parkinson’ s disease had been treated in the previous 8 weeks with selegilin e monotherapy (5 ± 10 mg/ day) or (in one case) with a combination of selegilin e (10 mg/day) and levodopa (375 mg/day), but who still met the DSM-III-R criteria1 3 for major depression were included in an 8-week clinical drug surveillanc e. The stage of Parkinson’ s disease before the start of citalopram treatment was determined from the 5-item Hoehn-Yahr Scale.1 4 The daily dose of citalopram was 20 mg in each case. The patients were seen every second week, and the severity of depression was evaluated at baseline (before citalopram treatment) and at week 8 on the 17-item Hamilton Depression Rating Scale (HDRS).1 5 Patients whose total
124
Z Rihmer et al
Table 1 Demographic and clinical characteristics of eight outpatients with Parkinson’s disease and major depression Age (yrs)
Sex
Hoehn-Yahr stage of Parkinson’s disease1 4
Somatic illness (medication)
1
70
M
2.0
2
76
F
2.0
3
75
M
2.0
hypertension (no medication) hypertension (captopril) prostatectomy
4
81
M
2.5
5
71
M
1.0
6
75
M
2.0
7
61
M
3.0
hypertension (captopril) ±
8
84
F
5.0
cholecystectomy
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Adelaide on 11/13/14 For personal use only.
No.
Daily dose (mg) of selegiline citalopram
hypertension (bopindolol) ±
Total HDRS score at week 0 at week 8
2´ 5
1 ´ 20
20
6
2´ 5
1 ´ 20
22
6
2´ 5
1 ´ 20
20
6
2´ 5
1 ´ 20
19
15**
2 ´ 2.5
1 ´ 20
20
9
2´ 5
1 ´ 20
22
8
2´ 5
1 ´ 20
19
4
2 ´ 5*
1 ´ 20
21
19**
*Received levodopa (375 mg/day) also **nonresponders
HDRS score dropped by over 50% at week 8 were classifie d as responders . A semi-structur ed interview on the adverse events/side-effect s was also addressed at each medical contact.
RESULTS AND DISCUSSION Table 1 shows the demographi c and clinical characteristic s of the patients, including somatic comorbidity and its treatment. Six patients had comorbid somatic illness (mostly hypertension ). The mean total HDRS score of the eight depressed patients was 20.4 at baseline and 9.1 at week 8. Six of the eight patients were classifie d as responders (i.e. more than 50% reduction of the total HDRS score at week 8). As expected, the patients tolerated the selegiline-ci talopram combination quite well, and no adverse events were reported or observed. One patient (Table 1, no. 1) had nausea and abdominal discomfort while he increased the daily dose of citalopram to 40 mg on his own initiative; these side-effect s disappeared when the citalopram was reduced to the original dose. It should be noted that one patient (Table 1, no. 7) showed mild hypomanic features 4 weeks after the end of the 8-week surveillanc e (at week 12), and become euthymic after the reduction of citalopram to 10 mg/day. The majority of patients (six out of the eight) responded well to citalopram treatment and no adverse events occurred during the 8-week clinical follow-up period. Although the small sample size and the open nature of this study limit the generalizabi lity of the results, our observations suggest that the combination of a low dose of selegilin e (5 ± 10 mg daily,
which is the dose generally used in Parkinson’ s disease) with a relatively low dose (20 mg/day) of citalopram (and possibly of other SSRIs) is an effective and safe treatment strategy for depression of patients with Parkinson’ s disease. Our findings also suggest that the general statement that coadministra tion of MAOIs and SSRIs is contraindicat ed4 ± 6 may not be precise. The combination of a low dose of selective MAO-B inhibitor (in the MAO-B selective range) with citalopram (or probably with other SSRIs) may be safe and effective in the treatment of depressio n in Parkinson’ s disease. Of course, our study needs confirmation in a larger sample of patients, for a longer period of time.
ACKNOWLEDGEMENTS This study was supported in part by Ministry of Welfare, Hungary (Grant ETT-T04 307/93 to Dr. Rihmer).
KEY POINTS
· · · ·
A high number of patients with Parkinson’ s disease also have depression The combination of low doses of selegilin e and citalopram is effective and safe treatment The general statement that coadministra tion of MAOIs and SSRIs is contraindicat ed may not be precise Because of the open nature and small sample size of this study further studies are needed
Selegiline and citalopram in Parkinson’s disease
125
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Adelaide on 11/13/14 For personal use only.
REFERENCES 1. Cummings JL (1992) Depression and Parkinson’s disease: a review. Am J Psychiatry 149: 443 ± 454. 2. Cunningham LA (1994) Depression in the medically ill: choosing an antidepressant. J Clin Psychiatry 55 (suppl A): 90 ± 97. 3. Leonard BE (1993) The comparative pharmacology on new antidepressants.J Clin Psychiatry 54 (suppl 8): 3 ± 15. 4. Lane R, Baldwin D, Preskorn S (1995) The SSRIs: advantages, disadvantages and differences. J Psychopharmac ol 9 (suppl): 163 ± 178. 5. Preskorn SH (1993) Pharmacokinetics of antidepressants: why and how they are relevant to treatment. J Clin Psychiatry 54 (suppl 9): 14 ± 34. 6. Warrington SJ (1992) Clinical implications of the pharmacology of serotonin reuptake inhibitors. Int Clin Psychopharma cology 7 (suppl 2) 13 ± 19. 7. Feighner JP, Boyer WF, Tyler DL et al (1991) Adverse consequences of fluoxetine-MAOI combination therapy. J Clin Psychiatry 52: 87 ± 8. 8. Sternbach H (1991) The serotonin syndrome. Am J Psychiatry 148: 705 ± 13.
9. Neuvonen PJ, Pohjola-Sintonen S, Tacke U et al (1993) Five fatal cases of serotonin syndrome after moclobemide-clomipramine overdoses. Lancet 342: 1419. 10. Schulz R, Antonin K-H, Hoffmann E et al (1989) Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline. Clin Pharmacol Ther 46: 528 ± 36. 11. Elsworth JD, Glover V, Reynolds GP (1978) Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the `cheese effect’. Psychopharmaco logy 57: 33 ± 8. 12. Suchowersky O, de Vires JD (1990) Interaction of fluoxetine and selegiline (letter) Canad J Psychiatry 35: 571 ± 2. 13. American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised (DSM-III-R). American Psychiatric Association, Washington, DC. 14. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17: 427 ± 42. 15. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56 ± 62.
2000 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2000 Volume 4 Pages 123 ± 125
123
Selegiline-citalopram combination in patients with Parkinson’s disease and major depression ZOLTAÂN RIHMER1 , MAÂRIA SAÂTORI 2 AND PEÂTER PESTALITY1 Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Adelaide on 11/13/14 For personal use only.
1
National Institute for Psychiatry and Neurology, and 2 Szent RoÂkus Hospital, Budapest, Hungary
Correspondence Address Dr. ZoltaÂn Rihmer, Budapest 27, POB 1, 1281 Hungary Tel/Fax: +36 1 391 53 53
Received 1 April 1999; revised 16 June 1999; accepted for publication 9 July 1999
INTRODUCTION:
We evaluated the efficacy and safety of the selegilinecitalopram combination in the treatment of major depression in patients with Parkinson’s disease. METHOD : Eight consecutive depressed outpatient s who had received previously selegiline monotherapy or (one patient) selegiline-levod opa combination (the dose of selegiline was 5-10 mg/day in each case) for mild to severe Parkinson’s disease were treated with 20 mg citalopram/day. The severity of depression was evaluated on the Hamilton Depression Rating Scale before and 8 weeks after citalopram treatment. RESULTS: The majority of the patients (six) responded well to citalopram treatment and no adverse events occurred. CONCLUSION : The combination of a low dose of selegiline (5-10 mg daily) and citalopram (20 mg daily) may be an effective and safe method in the treatment of major depression in patients with Parkinson’s disease. (Int J Psych Clin Pract 2000; 4: 123 ± 125) Keywords citalopram Parkinson’s disease combination therapy
INTRODUCTION
F
orty percent of patients with Parkinson’ s disease have clinical depression : a complication which results in a worse outcome and makes the treatment more difficult .1 Because of its favourable side-effect profile and low behavioural toxicity, the serotonin selective re-uptake inhibitor antidepressan ts (SSRIs) are promising drugs in the treatment of depression with Parkinson’ s disease.2 ,3 These patients are often on selegilin e (a selective MAO-B inhibitor) therapy because of their movement disorder. However, several review articles declare that one of the most potentially serious adverse interactions that can occur with the co-administra tion of SSRIs and MAOIs is the serious, even fatal, serotonin syndrome.4 ± 6 This is primarily true for the nonselective MAOIs such as phenelzine and tranylcypromi ne,7 ,8 and for the selective MAO-A inhibitor moclobemide.9 Selegiline is a selective MAO-B inhibitor, when given in low doses of 5 ± 20 mg/ day, and this increases the turnover of dopamine, but not of the serotonin and noradrenali ne level. However, in higher doses (30 mg/day or above), selegilin e loses its MAO-B selectivity and acts as a nonselective MAOI, inhibiting the degradation not only of dopamine, but also of serotonin and noradrenalin e,1 0 ,1 1 and in combination
depression selegiline
with SSRIs can cause serotonin syndrome .1 2 We report here the effectivenes s and safety of an SSRI-selegilin e combination for major depression in eight outpatients whose Parkinson’ s disease was previously treated with a low dose of selegilin e and who were still on selegilin e during the SSRI treatment.
PATIENTS AND METHODS Eight consecutive outpatients (all caucasians , 6M, 2F) aged between 61 and 84 years (mean 74.1), whose mild to moderate Parkinson’ s disease had been treated in the previous 8 weeks with selegilin e monotherapy (5 ± 10 mg/ day) or (in one case) with a combination of selegilin e (10 mg/day) and levodopa (375 mg/day), but who still met the DSM-III-R criteria1 3 for major depression were included in an 8-week clinical drug surveillanc e. The stage of Parkinson’ s disease before the start of citalopram treatment was determined from the 5-item Hoehn-Yahr Scale.1 4 The daily dose of citalopram was 20 mg in each case. The patients were seen every second week, and the severity of depression was evaluated at baseline (before citalopram treatment) and at week 8 on the 17-item Hamilton Depression Rating Scale (HDRS).1 5 Patients whose total
124
Z Rihmer et al
Table 1 Demographic and clinical characteristics of eight outpatients with Parkinson’s disease and major depression Age (yrs)
Sex
Hoehn-Yahr stage of Parkinson’s disease1 4
Somatic illness (medication)
1
70
M
2.0
2
76
F
2.0
3
75
M
2.0
hypertension (no medication) hypertension (captopril) prostatectomy
4
81
M
2.5
5
71
M
1.0
6
75
M
2.0
7
61
M
3.0
hypertension (captopril) ±
8
84
F
5.0
cholecystectomy
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Adelaide on 11/13/14 For personal use only.
No.
Daily dose (mg) of selegiline citalopram
hypertension (bopindolol) ±
Total HDRS score at week 0 at week 8
2´ 5
1 ´ 20
20
6
2´ 5
1 ´ 20
22
6
2´ 5
1 ´ 20
20
6
2´ 5
1 ´ 20
19
15**
2 ´ 2.5
1 ´ 20
20
9
2´ 5
1 ´ 20
22
8
2´ 5
1 ´ 20
19
4
2 ´ 5*
1 ´ 20
21
19**
*Received levodopa (375 mg/day) also **nonresponders
HDRS score dropped by over 50% at week 8 were classifie d as responders . A semi-structur ed interview on the adverse events/side-effect s was also addressed at each medical contact.
RESULTS AND DISCUSSION Table 1 shows the demographi c and clinical characteristic s of the patients, including somatic comorbidity and its treatment. Six patients had comorbid somatic illness (mostly hypertension ). The mean total HDRS score of the eight depressed patients was 20.4 at baseline and 9.1 at week 8. Six of the eight patients were classifie d as responders (i.e. more than 50% reduction of the total HDRS score at week 8). As expected, the patients tolerated the selegiline-ci talopram combination quite well, and no adverse events were reported or observed. One patient (Table 1, no. 1) had nausea and abdominal discomfort while he increased the daily dose of citalopram to 40 mg on his own initiative; these side-effect s disappeared when the citalopram was reduced to the original dose. It should be noted that one patient (Table 1, no. 7) showed mild hypomanic features 4 weeks after the end of the 8-week surveillanc e (at week 12), and become euthymic after the reduction of citalopram to 10 mg/day. The majority of patients (six out of the eight) responded well to citalopram treatment and no adverse events occurred during the 8-week clinical follow-up period. Although the small sample size and the open nature of this study limit the generalizabi lity of the results, our observations suggest that the combination of a low dose of selegilin e (5 ± 10 mg daily,
which is the dose generally used in Parkinson’ s disease) with a relatively low dose (20 mg/day) of citalopram (and possibly of other SSRIs) is an effective and safe treatment strategy for depression of patients with Parkinson’ s disease. Our findings also suggest that the general statement that coadministra tion of MAOIs and SSRIs is contraindicat ed4 ± 6 may not be precise. The combination of a low dose of selective MAO-B inhibitor (in the MAO-B selective range) with citalopram (or probably with other SSRIs) may be safe and effective in the treatment of depressio n in Parkinson’ s disease. Of course, our study needs confirmation in a larger sample of patients, for a longer period of time.
ACKNOWLEDGEMENTS This study was supported in part by Ministry of Welfare, Hungary (Grant ETT-T04 307/93 to Dr. Rihmer).
KEY POINTS
· · · ·
A high number of patients with Parkinson’ s disease also have depression The combination of low doses of selegilin e and citalopram is effective and safe treatment The general statement that coadministra tion of MAOIs and SSRIs is contraindicat ed may not be precise Because of the open nature and small sample size of this study further studies are needed
Selegiline and citalopram in Parkinson’s disease
125
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of Adelaide on 11/13/14 For personal use only.
REFERENCES 1. Cummings JL (1992) Depression and Parkinson’s disease: a review. Am J Psychiatry 149: 443 ± 454. 2. Cunningham LA (1994) Depression in the medically ill: choosing an antidepressant. J Clin Psychiatry 55 (suppl A): 90 ± 97. 3. Leonard BE (1993) The comparative pharmacology on new antidepressants.J Clin Psychiatry 54 (suppl 8): 3 ± 15. 4. Lane R, Baldwin D, Preskorn S (1995) The SSRIs: advantages, disadvantages and differences. J Psychopharmac ol 9 (suppl): 163 ± 178. 5. Preskorn SH (1993) Pharmacokinetics of antidepressants: why and how they are relevant to treatment. J Clin Psychiatry 54 (suppl 9): 14 ± 34. 6. Warrington SJ (1992) Clinical implications of the pharmacology of serotonin reuptake inhibitors. Int Clin Psychopharma cology 7 (suppl 2) 13 ± 19. 7. Feighner JP, Boyer WF, Tyler DL et al (1991) Adverse consequences of fluoxetine-MAOI combination therapy. J Clin Psychiatry 52: 87 ± 8. 8. Sternbach H (1991) The serotonin syndrome. Am J Psychiatry 148: 705 ± 13.
9. Neuvonen PJ, Pohjola-Sintonen S, Tacke U et al (1993) Five fatal cases of serotonin syndrome after moclobemide-clomipramine overdoses. Lancet 342: 1419. 10. Schulz R, Antonin K-H, Hoffmann E et al (1989) Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline. Clin Pharmacol Ther 46: 528 ± 36. 11. Elsworth JD, Glover V, Reynolds GP (1978) Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the `cheese effect’. Psychopharmaco logy 57: 33 ± 8. 12. Suchowersky O, de Vires JD (1990) Interaction of fluoxetine and selegiline (letter) Canad J Psychiatry 35: 571 ± 2. 13. American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised (DSM-III-R). American Psychiatric Association, Washington, DC. 14. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17: 427 ± 42. 15. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56 ± 62.
