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HYPOKALAEMIA IN PATIENTS WITH ACUTE MYELOID LEUKAEMIA AFTER TREATMENT WITH FLUCONAZOLE
1017
significant fall a direct antiglobulin test should be done. This policy may reveal whether the reaction in
our
patient
was
unique
or
whether this adverse effect is one that should be borne in mind in the
generality of cases of streptokinase therapy for AMI. Regional Centre for Blood Transfusion and Clinical Immunology, Aalborg Hospital,
DK-9100 Aalborg, Denmark
OLE MATHIESEN N. GRUNNET
1. ISIS-2. Randomised tnal of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction. Lancet 1988; ii: 349-60. 2. Issitt PT. Applied blood group serology Miami: Montgomery Scientific Publications, 1985: 554.
HYPOKALAEMIA IN PATIENTS WITH ACUTE MYELOID LEUKAEMIA AFTER TREATMENT WITH FLUCONAZOLE
SiR,—In non-neutropenic patients the frequency of adverse to fluconazole is low. However, we have seen hypokalaemia in three patients with acute myeloid leukaemia who were neutropenic and were receiving fluconazole. Patients 1 (M/66) and 2 (F/53) had completed induction chemotherapy with daunorubicin for 3 days and cytosine for 7 days. Both patients became pancytopenic and had bacterial infections confirmed by blood culture. In addition, they were receiving routine oral prophylaxis with nystatin mouth-washes and amphotericin lozenges. Because their temperature remained elevated despite appropriate antibiotic therapy fluconazole 50 mg orally in the morning was started. Hypokalaemia developed in both patients within 2-3 days. Patient 1 received fluconazole for 12 days. Potassium dropped from 4-1-5 mmol/1 before fluconazole therapy to 26 mmol/1, despite oral potassium replacement therapy. 3 days after stopping fluconazole potassium rose from 3-0 to 43 mmol/1. In patient 2 potassium of 3mmol/1 before fluconazole therapy fell to 17 mmol/13 3 days after starting the drug. Fluconazole was stopped reactions
and potassium then rose above 28 mmol/l. Patient 3 had acute myeloid leukaemia in chronic relapse with local infiltration of her tongue. After local radiotherapy intensive antifungal prophylaxis was indicated and she was started on oral fluconazole 50 mg in the morning for 3 weeks. Potassium fell from 35-4 to 2-5-3 mmol/1, and she required potassium supplementation. After reduction of fluconazole dose to 50 mg on alternate days potassium rose to above 30 mmol/1 but fell again when oral pharyngeal candidiasis developed and her fluconazole was increased to 50 mg daily. We have also used fluconazole in two patients with Hodgkin’s disease who were rendered pancytopenic by intensive chemotherapy. Serum potassium concentration did not fall during fluconazole therapy. Oral fluconazole therapy in patients with acute myeloid leukaemia should only be used with careful monitoring of serum
potassium.
Department of Haematology, Belfast City Hospital, Belfast BT9 7AD
D. KIDD E. A. RANAGHAN T. C. M. MORRIS
SEVERE ANOREXIA AND POSSIBLE PSYCHOSIS OR HYPOMANIA AFTER TRAZODONE-TRYPTOPHAN TREATMENT OF AGGRESSION about the use of trazodone-tryptophan for aggressive behaviours in patients with dementia, organic mental disorders, and mental retardation have been encouraging.l-s However, this combination may precipitate further problems. We report a female patient whose aggressive behaviour ceased with this therapy but she also stopped eating and possibly became psychotic
SIR,-Reports
or
hypomanic.
The patient, age 29, was admitted to the state hospital at age 17 from a facility for mentally retarded patients because of behaviour outbursts uncontrolled by several trials of neuroleptics. The initial diagnoses on admission included undifferentiated schizophrenia, mild mental retardation, and several congenital defects. However,
because of the mental retardation it has been difficult to document the presence of psychotic symptoms. Aggressive behaviours have included attacks on staff and other patients, destruction of furniture, and self-abuse, especially to her eyes causing retinal detachment. Trials of several neuroleptics, carbamazepine, clonazepam, lowdose propranolol, and lithium have had little success in altering these outbursts. A recent trial of clonazepam, up to 105 mg daily, seemed mildly beneficial. Trazodone and tryptophan were added in an attempt to provide further control. The doses were gradually increased over a 3 week period up to 100 mg and 500 mg, respectively, both three times a week. At this point the aggressive behaviour stopped. Within 2 weeks the patient stopped eating and she lost 4kg in 3 weeks. She also had symptoms of possible psychosis or hypomania. Soon after she became drowsy and withdrawn. Plasma drug levels at this time were: trazodone 900 ng/ml (reference range, 800-1600), tryptophan 1-3 mg/dl (1-4-30), and clonazepam 102 ltg/ml (20-60). Trazodone and tryptophan were discontinued immediately and clonazepam decreased to 8 mg daily followed by a tapered reduction schedule. Within 6 days the patient was again aggressive toward staff, throwing furniture, and attempting to hurt herself. Trazodone and tryptophan were restarted at lower doses while clonazepam continued to be tapered. Cyproheptadine was also started in an attempt to stimulate appetite. The patient’s eating patterns gradually improved and aggressive behaviours again decreased. She then began to display further symptoms of psychosis, appearing to respond to voices. All medications were discontinued and lithium was started followed by low-dose haloperidol. The aggressive behaviours of this patient seemed to respond
dramatically to trazodone-tryptophan treatment. Although mildly drowsy, the patient became pleasant, without her usual outbursts. Aggression has been linked to serotonin hypoactivity, and drugs with serotoninergic activity have been successfully used to treat aggression.6 Serotonin is also associated with appetite control. This patient is now being treated with tryptophan and chlorpromazine. She has occasional aggressive outbursts and her eating patterns are adequate. Unfortunately it has been impossible to achieve complete remission of aggression with reduced doses of trazodone and tryptophan without inducing the problems we report. North Dakota State Hospital, Jamestown, North Dakota 58401, USA
BETTY D. PATTERSON MONGKOL M. SRISOPARK
1. Greenwald BS, Marin DB, Silverman SM.
2.
Serotoninergic treatment of screaming and banging in dementia. Lancet 1986; ii: 1464-65. O’Neil M, Page N, Adkins WN, Eichelman B. Tryptophan-trazodone treatment of
aggressive behaviour. Lancet 1986; ii: 859-60. GK, Stevens J, Perkms A. Trazodone/tryptophan for aggressive behaviour. Lancet 1987; i: 929-30. 4. Simpson DM, Foster D. Improvement m organically disturbed behaviour with trazodone treatment J Clin Psychiatry 1986; 47: 191-93. 5. Pinner E, Rich CL Effects of trazodone on aggressive behavior in seven patients with organic mental disorders. AmJ Psychiatry 1988; 145: 1295-96. 6. Eichelman B. Neurochemical and psychopharmacologic aspects of aggressive behavior. In: Meltzer H, ed. Psychopharmacology. the third generation of progress. New York Raven Press, 1987: 697-704. 7. Hyman SL, Coyle JT, Parke JC, et al. Anorexia and altered serotonin metabolism in a patient with argininosuccinic aciduria. J Pediatr 1986; 108: 705-09. 3. Wilcock
A NEW TREATMENT FOR ENDOMETRIOSIS
SIR,-LHRH agonist analogues and danazol have similar efficacy in the treatment of endometriosis." Unfortunately both treatments have unpleasant side-effects. In one study3 85% of patients treated with danazol complained of troublesome sideeffects, which are due to the drug’s androgenic properties, including weight gain, oedema, myalgia, acne, decrease in breast size, hirsutism, and deepening of the voice. The hypo-oestrogenism that is a consequence of LHRH analogue treatment causes hot flushes, vaginal dryness, and a decrease in libido. Moreover, the risk of bone mineral loss’ and possible changes in lipid metabolisml discourage prolonged use of LHRH analogues. The suppression of serum oestradiol is greater with LHRH analogues than with danazol. The degree of ovarian suppression
significant fall a direct antiglobulin test should be done. This policy may reveal whether the reaction in
our
patient
was
unique
or
whether this adverse effect is one that should be borne in mind in the
generality of cases of streptokinase therapy for AMI. Regional Centre for Blood Transfusion and Clinical Immunology, Aalborg Hospital,
DK-9100 Aalborg, Denmark
OLE MATHIESEN N. GRUNNET
1. ISIS-2. Randomised tnal of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction. Lancet 1988; ii: 349-60. 2. Issitt PT. Applied blood group serology Miami: Montgomery Scientific Publications, 1985: 554.
HYPOKALAEMIA IN PATIENTS WITH ACUTE MYELOID LEUKAEMIA AFTER TREATMENT WITH FLUCONAZOLE
SiR,—In non-neutropenic patients the frequency of adverse to fluconazole is low. However, we have seen hypokalaemia in three patients with acute myeloid leukaemia who were neutropenic and were receiving fluconazole. Patients 1 (M/66) and 2 (F/53) had completed induction chemotherapy with daunorubicin for 3 days and cytosine for 7 days. Both patients became pancytopenic and had bacterial infections confirmed by blood culture. In addition, they were receiving routine oral prophylaxis with nystatin mouth-washes and amphotericin lozenges. Because their temperature remained elevated despite appropriate antibiotic therapy fluconazole 50 mg orally in the morning was started. Hypokalaemia developed in both patients within 2-3 days. Patient 1 received fluconazole for 12 days. Potassium dropped from 4-1-5 mmol/1 before fluconazole therapy to 26 mmol/1, despite oral potassium replacement therapy. 3 days after stopping fluconazole potassium rose from 3-0 to 43 mmol/1. In patient 2 potassium of 3mmol/1 before fluconazole therapy fell to 17 mmol/13 3 days after starting the drug. Fluconazole was stopped reactions
and potassium then rose above 28 mmol/l. Patient 3 had acute myeloid leukaemia in chronic relapse with local infiltration of her tongue. After local radiotherapy intensive antifungal prophylaxis was indicated and she was started on oral fluconazole 50 mg in the morning for 3 weeks. Potassium fell from 35-4 to 2-5-3 mmol/1, and she required potassium supplementation. After reduction of fluconazole dose to 50 mg on alternate days potassium rose to above 30 mmol/1 but fell again when oral pharyngeal candidiasis developed and her fluconazole was increased to 50 mg daily. We have also used fluconazole in two patients with Hodgkin’s disease who were rendered pancytopenic by intensive chemotherapy. Serum potassium concentration did not fall during fluconazole therapy. Oral fluconazole therapy in patients with acute myeloid leukaemia should only be used with careful monitoring of serum
potassium.
Department of Haematology, Belfast City Hospital, Belfast BT9 7AD
D. KIDD E. A. RANAGHAN T. C. M. MORRIS
SEVERE ANOREXIA AND POSSIBLE PSYCHOSIS OR HYPOMANIA AFTER TRAZODONE-TRYPTOPHAN TREATMENT OF AGGRESSION about the use of trazodone-tryptophan for aggressive behaviours in patients with dementia, organic mental disorders, and mental retardation have been encouraging.l-s However, this combination may precipitate further problems. We report a female patient whose aggressive behaviour ceased with this therapy but she also stopped eating and possibly became psychotic
SIR,-Reports
or
hypomanic.
The patient, age 29, was admitted to the state hospital at age 17 from a facility for mentally retarded patients because of behaviour outbursts uncontrolled by several trials of neuroleptics. The initial diagnoses on admission included undifferentiated schizophrenia, mild mental retardation, and several congenital defects. However,
because of the mental retardation it has been difficult to document the presence of psychotic symptoms. Aggressive behaviours have included attacks on staff and other patients, destruction of furniture, and self-abuse, especially to her eyes causing retinal detachment. Trials of several neuroleptics, carbamazepine, clonazepam, lowdose propranolol, and lithium have had little success in altering these outbursts. A recent trial of clonazepam, up to 105 mg daily, seemed mildly beneficial. Trazodone and tryptophan were added in an attempt to provide further control. The doses were gradually increased over a 3 week period up to 100 mg and 500 mg, respectively, both three times a week. At this point the aggressive behaviour stopped. Within 2 weeks the patient stopped eating and she lost 4kg in 3 weeks. She also had symptoms of possible psychosis or hypomania. Soon after she became drowsy and withdrawn. Plasma drug levels at this time were: trazodone 900 ng/ml (reference range, 800-1600), tryptophan 1-3 mg/dl (1-4-30), and clonazepam 102 ltg/ml (20-60). Trazodone and tryptophan were discontinued immediately and clonazepam decreased to 8 mg daily followed by a tapered reduction schedule. Within 6 days the patient was again aggressive toward staff, throwing furniture, and attempting to hurt herself. Trazodone and tryptophan were restarted at lower doses while clonazepam continued to be tapered. Cyproheptadine was also started in an attempt to stimulate appetite. The patient’s eating patterns gradually improved and aggressive behaviours again decreased. She then began to display further symptoms of psychosis, appearing to respond to voices. All medications were discontinued and lithium was started followed by low-dose haloperidol. The aggressive behaviours of this patient seemed to respond
dramatically to trazodone-tryptophan treatment. Although mildly drowsy, the patient became pleasant, without her usual outbursts. Aggression has been linked to serotonin hypoactivity, and drugs with serotoninergic activity have been successfully used to treat aggression.6 Serotonin is also associated with appetite control. This patient is now being treated with tryptophan and chlorpromazine. She has occasional aggressive outbursts and her eating patterns are adequate. Unfortunately it has been impossible to achieve complete remission of aggression with reduced doses of trazodone and tryptophan without inducing the problems we report. North Dakota State Hospital, Jamestown, North Dakota 58401, USA
BETTY D. PATTERSON MONGKOL M. SRISOPARK
1. Greenwald BS, Marin DB, Silverman SM.
2.
Serotoninergic treatment of screaming and banging in dementia. Lancet 1986; ii: 1464-65. O’Neil M, Page N, Adkins WN, Eichelman B. Tryptophan-trazodone treatment of
aggressive behaviour. Lancet 1986; ii: 859-60. GK, Stevens J, Perkms A. Trazodone/tryptophan for aggressive behaviour. Lancet 1987; i: 929-30. 4. Simpson DM, Foster D. Improvement m organically disturbed behaviour with trazodone treatment J Clin Psychiatry 1986; 47: 191-93. 5. Pinner E, Rich CL Effects of trazodone on aggressive behavior in seven patients with organic mental disorders. AmJ Psychiatry 1988; 145: 1295-96. 6. Eichelman B. Neurochemical and psychopharmacologic aspects of aggressive behavior. In: Meltzer H, ed. Psychopharmacology. the third generation of progress. New York Raven Press, 1987: 697-704. 7. Hyman SL, Coyle JT, Parke JC, et al. Anorexia and altered serotonin metabolism in a patient with argininosuccinic aciduria. J Pediatr 1986; 108: 705-09. 3. Wilcock
A NEW TREATMENT FOR ENDOMETRIOSIS
SIR,-LHRH agonist analogues and danazol have similar efficacy in the treatment of endometriosis." Unfortunately both treatments have unpleasant side-effects. In one study3 85% of patients treated with danazol complained of troublesome sideeffects, which are due to the drug’s androgenic properties, including weight gain, oedema, myalgia, acne, decrease in breast size, hirsutism, and deepening of the voice. The hypo-oestrogenism that is a consequence of LHRH analogue treatment causes hot flushes, vaginal dryness, and a decrease in libido. Moreover, the risk of bone mineral loss’ and possible changes in lipid metabolisml discourage prolonged use of LHRH analogues. The suppression of serum oestradiol is greater with LHRH analogues than with danazol. The degree of ovarian suppression