A 70 year old woman, who has been taking tranquillizers for 25 years, was referred to the psychiatr

Fråga: A 70 year old woman, who has been taking tranquillizers for 25 years, was referred to the psychiatrist in order to lower the dose of the medication. She was taking amitriptyline (Saroten) 50 mg/day, levomepromazine (Nozinan) 50 mg/day and propiomazine (Propavan) 50 mg/day. Now she is on trimipramine (Surmontil) 2-4 tablets/day (50-100 mg) and flunitrazepam (Rohypnol) 2 tablets/day (2 mg). She also takes amitriptyline (50 mg) on her own, and still has difficulty sleeping. The patient has had leucopenia (2.7-3.4) for many years. Her last value was 2.0, with a normal differential count. Other medication: alprenolol (Aptin), nicotinic acid (Hexanicit) and nitroglycerine.

The doctor would like to know: 1) Whether there is an increased risk for agranulocytosis when two tricyclics are used in combination.

2) Whether clomethiazole can cause any blood dyscrasias.

Sammanfattning: Agranulocytosis is a rare side effect of tricyclic antidepressants when used in monotherapy.

No blood dyscrasias have been reported with the use of clomethiazol.

Svar: Drug induced granulocytopenia is a rare complication of tricyclic antidepressant therapy (1-4) but phenothiazines are more frequently implicated.

Agranulocytosis and less severe neutropenia have been reported with the use of nearly all tricyclics including trimipramine and amitriptyline (2,5).

The mechanism is still unknown - both immune, and direct toxic effects have been proposed. It can appear between 4-7 weeks after onset of treatment (1,4).

There seems to be an increased risk when other drugs such as phenothiazines are being co-administered (1,4).

No study of adverse reactions with combined tricyclic therapy has been found in the literature.

There are no reports in the literature from 1966 to 1987 about blood dyscrasias associated with the use of clomethiazol. 1 Albertini RS, Penders TM: Agranulocytosis associated with tricyclics. J Clin Psychiatry 1978; 39: 483-485

2 Davies, Textbook of adverse drug reactions, 1985; 3rd ed
3 Gravenor DS, Leclerc JR, Blake G: Tricyclic antidepressant agranulocytosis. Can J Psychiatry 1986; 31: 661
4 d´Arcy, Iatrogenic diseases, 1986

5 Socialstyrelsens biverkningsregister, 1965-1987