Is there any documentation of combined treatment with nefazodone (Nefadar) and amitriptyline (Trypt

Fråga: Is there any documentation of combined treatment with nefazodone (Nefadar) and amitriptyline (Tryptizol)?

A depressed patient has treated himself with 50-75 mg of nefazodone and 75 mg of amitriptyline and claims not to have any side effects. The patient is also treated with buspirone (Buspar).

Sammanfattning: No studies of nefazodone in combination with amitriptyline have been found. As pharmacokinetic interactions may occur it is recommended that therapeutic drug monitoring should be done.

Svar: In a search of Drugline, Medline and reference literature, no studies of nefazodone in combination with amitriptyline in depressive disease were found.

Nefazodone, an antidepressive drug which is a combined 5-HT2 antagonist and 5-HT reuptake inhibitor is mainly metabolised by the enzyme CYP3A4 to three pharmacologically active metabolites. One of these (mCPP) is further metabolised by the enzyme CYP2D6 and is a weak inhibitor of CYP2D6. Nefazodone is a weak inhibitor of CYP2D6 and CYP3A4 (1, 2). Amitriptyline, a tricyclic antidepressant, is a noradrenaline and 5-HT reuptake inhibitor. It is metabolised by CYP2D6 and CYP1A2 (2, 3). Buspirone, an anxiolytic agent, is a partial agonist of postsynaptic 5-HT1A receptors and a full agonist of presynaptic 5HT1A autoreceptors and an antagonist of dopamine (D2) receptors. It is metabolised by CYP3A4. Buspirone has a wide therapeutic interval (4).

As nefazodone, amitriptyline and buspirone are metabolised by the same enzyme system it is possible that they interact so that higher levels of these drugs may be obtained. However, no studies support that conclusion. Thus it is recommended that if this treatment is continued, therapeutic drug monitoring should be done. Amitriptyline is analysed at the department of Clinical Pharmacology, Huddinge hospital, and buspirone and nefazodone is analysed at the department of Clinical Pharmacology, Lund. 1 Drugline no 15244 (year 1999) 2 FASS 1999 (The Swedish catalogue of approved medical products) 3 Drugline no 12910 (year 1996) 4 Drugline no 13341 (year 1997)