Posted by ed_uk on November 3, 2004, at 12:22:01
In reply to what are potent interact b/t L-deprenyl Prozac?, posted by 3 Beer Effect on November 1, 2004, at 20:33:58
To 3 beer effect....
Here is some info about the interaction between selegiline(deprenyl) and antidepressants...........Selegiline + Antidepressants
A few cases of the serotonin syndrome and other serious CNS disturbances have been seen with selegiline and tricyclic antidepressants or SSRIs. One of the makers of selegiline contraindicates its use with any antidepressant drug, while another advises avoiding SSRIs and venlafaxine, and using caution with the tricyclics.
Clinical evidence
A. SSRIs
(a) Citalopram
A double-blind randomised study in 18 healthy subjects found no important pharmacokinetic or pharmacodynamic interactions between citalopram and selegiline. Healthy subjects were given 20 mg citalopram or a placebo daily for 10 days followed by 4 days with concurrent selegiline 10 mg daily. There was no evidence of changes in vital signs or in the frequency of adverse events, but the bioavailability of the selegiline was slightly reduced by about 30% in the presence of citalopram. The authors of this report concluded that no clinically relevant interaction occurred between selegiline and citalopram. 1(b) Fluoxetine
A woman with Parkinson’s disease on selegiline, bromocriptine and levodopa/carbidopa was additionally started on fluoxetine 20 mg. Several days later she developed episodes of shivering and sweating in the mid-afternoon, which lasted several hours. Her hands became blue, cold and mottled and her blood pressure was elevated (200/120 mmHg). These episodes disappeared when both fluoxetine and selegiline were stopped, and did not reappear when the fluoxetine was restarted. 2Other similar patients have become hyperactive and apparently manic, 2 have developed ataxia, 3 or developed a tonic-clonic seizure and headache, flushes, palpitations, and a blood pressure of 250/130 mmHg (a pseudophaeochromocytoma syndrome), 4 all after the concurrent use of fluoxetine and selegiline. A possible serotonin syndrome has been described in another patient. 5 These reports contrast with a retrospective study of 23 patients with parkinsonism, who received both selegiline and fluoxetine without any serious side-effects occurring, although worsening confusion was noted in 5 patients. 6
(c) Paroxetine
A retrospective study of patients with Parkinson’s disease on selegiline 5 to 10 mg daily (and other antiparkinsonian drugs such as levodopa/carbidopa, bromocriptine, amantadine, pergolide, anticholinergics) noted that the addition of paroxetine 10 to 40 mg daily caused no adverse effects and the patients appeared to obtain overall benefit, including some improvement in parkinsonian symptoms. 7(d) Sertraline
A retrospective study of patients with Parkinson’s disease on selegiline 5 to 10 mg daily (and other antiparkinsonian drugs such as levodopa/carbidopa, bromocriptine, amantadine, pergolide, anticholinergics) noted that the addition of sertraline 25 to 100 mg daily caused no adverse effects and the patients appeared to obtain overall benefit, including some improvement in parkinsonian symptoms. 7B. Tetracyclic antidepressants
There is an isolated case report of a man on selegiline, levodopa/carbidopa, lisuride, maprotiline, theophylline and ephedrine who developed hypertensive crises (blood pressure up to 300/150 mmHg), intense vasoconstriction, confusion, abdominal pain, sweating, and tachycardia (110 bpm) within 2 days of raising the doses of theophylline and ephedrine. All of the drugs were stopped, and the patient was treated with intravenous nicardipine. He recovered uneventfully. It is thought that this ‘pseudophaeochromocytoma’ was due to a selegiline/maprotiline/ephedrine interaction. 8C. Tricyclic antidepressants
Between 1989 and 1994 the FDA in the USA received 16 reports of adverse interactions between selegiline and tricyclic antidepressants, which were attributed to the serotonin syndrome. For this reason the US labelling for selegiline suggests that concurrent use should be avoided. 9One of the makers of selegiline in the UK issues a warning suggesting caution 10 and another maker issues a contraindication. 11 They very briefly describe severe CNS toxicity in one patient given selegiline and amitriptyline (hyperpyrexia and death), and in another given protriptyline (tremor, agitation, restlessness, followed by unresponsiveness and death). 10,11 A further report describes the serotonin syndrome in a woman given nortriptyline and selegiline concurrently. 12
However, these warnings need to be balanced by other reports indicating that these reactions are uncommon. One study based on the findings of 45 investigators treating 4,568 patients with selegiline and antidepressants (not specifically named but possibly including the tricyclics) found that only 11 patients (0.24%) experienced symptoms considered to represent the serotonin syndrome, and only 2 patients (0.04%) experienced symptoms considered to be serious. 13 Another small retrospective study designed to evaluate the tolerability and efficacy of combining selegiline and tricyclic antidepressants (not specifically named) identified 28 patients who had taken both drugs. 9 In total, 17 patients definitely benefited and 6 patients possibly benefited from taking the combination. Another retrospective study of 25 occasions of combined tricyclic-selegiline use found no cases of the serotonin syndrome. 5
D. Miscellaneous antidepressants
(a) Trazodone
A retrospective study of patients with Parkinson’s disease on selegiline 5 to 10 mg daily (and other anti-parkinson drugs such as levodopa/carbidopa, bromocriptine, amantadine, pergolide, anticholinergics) noted that the addition of trazodone 25 to 150 mg daily caused no adverse effects and the patients appeared to obtain overall benefit, including some improvement in parkinsonian symptoms. 7(b) Venlafaxine
A man developed the serotonin syndrome 15 days after stopping selegiline 50 mg [daily] and within 30 minutes of starting venlafaxine 37.5 mg. 14Mechanism
Not fully understood. In some cases the symptoms seen appear to be consistent with the serotonin-syndrome, which is typified by CNS irritability, increased muscle tone, shivering, altered consciousness and myoclonus.Importance and management
The situation with selegiline and fluoxetine is by no means clear cut, because they have been used together apparently safely and uneventfully in some patients, 6 and only a few of the cases cited above 2,5 seem to fit the serotonin syndrome. The makers of selegiline say that the addition of fluoxetine, paroxetine, sertraline or venlafaxine has resulted in a variety of adverse reactions including diaphoresis, flushing, ataxia, tremor, hyperthermia, hyper/hypotension, seizures, palpitation, dizziness and mental changes that include agitation, confusion and hallucinations progressing to delirium and coma, and they recommend that these drug combinations should be avoided. 10,11If the decision is made to combine selegiline and any of the tricyclic antidepressants, the outcome should be well monitored but the likelihood of problems seems to be small. Nevertheless, one of the makers of selegiline contraindicates tricyclic antidepressants with selegiline, and in fact contraindicates all antidepressant drug combinations. 11
1. Laine K, Anttila M, Heinonen E, Helminen A, Huupponen R, Mäki-Ikola O, Reinikainen K, Scheinin M. Lack of adverse interactions between concomitantly administered selegiline and citalopram. Clin Neuropharmacol (1997) 20, 419–33.
2. Suchowersky O, deVries JD. Interaction of fluoxetine and selegiline. Can J Psychiatry (1990) 35, 571–2.
3. Jermain DM, Hughes PL, Follender AB. Potential fluoxetine-selegiline interaction. Ann Pharmacother (1992) 26, 1300.
4. Montastruc JL, Chamontin B, Senard JM, Tran MA, Rascol O, Llau ME, Rascol A. Pseudophaeochromocytoma in parkinsonian patient treated with fluoxetine plus selegiline. Lancet (1993) 341, 555.
5. Ritter JL, Alexander B. Retrospective study of selegiline-antidepressant drug interactions and a review of the literature. Ann Clin Psychiatry (1997) 9, 7–13.
6. Waters CH. Fluoxetine and selegiline — lack of significant interaction. Can J Neurol Sci (1994) 21, 259–61.
7. Toyama SC, Iacono RP. Is it safe to combine a selective serotonin reuptake inhibitor with selegiline? Ann Pharmacother (1994) 28, 405–6.
8. Lefebvre H, Noblet C, Moore N, Wolf LM. Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline. Clin Endocrinol (Oxf) (1995) 42, 95–9.
9. Yu LJ, Zweig RM. Successful combination of selegiline and antidepressants in Parkinson’s disease. Neurology (1996) 46 (2 Suppl), A374.
10. Eldepryl (Selegiline). Orion Pharma UK Ltd. Summary of product characteristics, December 1999.
11. Zelapar (Selegiline). Elan Pharma Ltd. Summary of product characteristics, December 1999.
12. Hinds NP, Hillier CEM, Wiles CM. Possible serotonin syndrome arising from an interaction between nortriptyline and selegiline in a lady with parkinsonism. J Neurol (2000) 247, 811.
13. Richard I, Kurlan R, Tanner C. Serotonin syndrome and the combined use of Deprenyl and an antidepressant in Parkinson’s disease. Neurology (1996) 46 (2 Suppl), A374.
14. Gitlin MJ. Venlafaxine, monoamine oxidase inhibitors, and the serotonin syndrome. J Clin Psychopharmacol (1997) 17, 66–67.
Hope this helps......
Ed.
poster:ed_uk
thread:410350
URL: http://www.dr-bob.org/babble/20041103/msgs/411096.html