Am
J Psychiatry
Tricyclic BY
/35:/I,
November
Overdose
KERRIN
/978
CLINICAL
in a Patient
WHITE,
Given
Combined
Tricyclic-MAOI
RESEARCH
REPORTS
Treatment
M.D
ature was 98#{176}. He was described as being in stage 1 coma, i.e. , purposefully responsive to painful stimuli. His skin appeared flushed, especially over the lower extremities. Reflexes were normal. An ECG showed right bundle branch block. A complete blood count was normal except for dcvated white count (14,800), serum electrolytes were normal except for elevated uric acid (8.3), and serum liver function tests were normal except for elevated creatinine phosphokinase (810). The patient awoke the next day, depressed but otherwise without adverse after-effects and with no further abnormality.
Recent reviews have documented the safety of combining monoamine oxidase inhibitors (MAOIs) and tncyclic antidepressants, particularly if one avoids parenteral medications, use of imipramine, or the delayed addition of tnicyclics to established MAOI treatment (1-3). Reported overdoses have formed part of the ‘evidence’ against use of tricyclic-MAOI combinations (4-8). Reviewing fatal versus nonfatal overdoses involving both MAOIs and tricyclics, Ananth and Luchins (3) remarked, ‘In none of the non-fatal overdose cases was the patient on a course of MAOIs before taking the tricyclics. In this paper I will describe such a case, in part to offset the alarm evoked by earlien reports, since fear offatal reactions has prevented controlled research in this area for too long. ‘
AND
‘
‘
Discussion
‘ ‘
Case
This patient, tnicyclic-MAOI and presented
after more than a month of combined treatment overdosed on the tnicyclic a clinical picture consistent with typical tricyclic overdose. No hypertension, hyperthermia, or seizures occurred. This observation contrasts with the few catastrophic case reports of similar overdose situations, which have contributed to the bias against such combination therapy. It seems significant that the tncyclic overdose occurred in a patient already on the MAOI reputed to be most dangerous, tranylcypromine. On the other hand, this overdose involved doxepin, a drug not (to my knowledge) previously implicated in presumed adverse reactions to combination therapy. Although part of the explanation may be the more recent introduction ofdoxepin, this drug has certainly been combined with MAOIs before, as cvidenced by Ayd’s survey (9) of55 such cases, all apparently without untoward effect. Perhaps doxepin should supersede amitniptyline as a drug of choice for combination with MAOIs. Although this one case cannot prove that such combination therapy poses no special risks to patients who overdose, it is encouraging to those interested in combination therapy to know that one such overdose occurred without unusual consequences. Too often we pay attention to the rare disaster while losing sight of the less dramatic, more commonplace course of events.
Report
A 21-year-old man was admitted with the chief complaint of hearing the voice of a dead friend telling him to kill himself.
For
the
he had
been
received
one
previous
6 months,
intermittently
chlorpromazine
previous
and
psychiatric
fore this admission, sleeping and a 9. 1-kg
When
he was
admitted
after
the
depressed
death
and
amitriptyline
in day
hospitalization. he stopped weight loss,
A few
treatment, and began
he appeared
ofthis
suicidal
friend,
and care
weeks
had
and
in
be-
suffered fitful to hallucinate.
depressed,
hostile,
and
suicidal. Physician examination revealed no pathology other than obesity and chronic bronchitis. Complete blood count, serum electrolytes, and serum liver function tests were all essentially normal.
In part tyline,
because
he was
of his history
of poor
response
to amitrip-
started
on tranylcypromine, 10 mg q.a.m. , and doxepin, 50 mg q.h.s. ; gradually increased to tranylcypromine, 20 mg at 6:00 p.m. , and doxepin, 150 mg q.h.s. He complained mainly of drowsiness and dry mouth but also had a stiff neck (relieved by diazepam), nausea, and vomiting. Blood pressure, recorded daily, never rose above 140/ 100. After 17 days on this treatment, he began to improve, and 17 days later he was discharged with a 2-week supply of
both medications. Two days after scious. unknown memory
When
his discharge,
the police
found
him uncon-
He
had made a suicide attempt by overdosing on an quantity of doxepin. He later persistently denied of the events#{231}imrnediately preceding his overdose.
he was
first
examined
by paramedics,
his pulse
rate
REFERENCES
was I 10 per blood pressure stricted, with
minute, respiratory rate 40 per minute, and 1 14/80. His pupils were equal and conslow response to light and dysconjugate gaze. On admission to our medical unit, within 3 hours after the police found him, he was lavaged and pink capsules were recovered. Pulse rate was 1 10 and regular, respirations were 36 and regular, blood pressure was 130/72 and his temper-
1. Schuckit M, Robins E, Feighner J: Tricyclic antidepressants and monoamine oxidase inhibitors. Arch Gen Psychiatry 24:509-514, 1971 2. Spiker DG, Pugh DD: Combining tricyclic and monoamine oxidase inhibitor antidepressants. Arch Gen Psychiatry 33:828-. 830,
1976
3. Ananth therapy.
Dr. White is Assistant Professor of Psychiatry, ty-University of Southern California Medical Place, Los Angeles, Calif. 90033.
0002-953X/78/001
Los Center,
1$0.35
©
Compr
D: A review Psychiatry
ofcombined
18:221-230,
tricyclic
and MAOI
1977
4. Ayd FJ: Toxic somatic and psychopathologic reactions to antidepressant drugs. J Neuropsychiatry 2: 1 19-122, 1961 5. Luby ED, Domino EF: Toxicity from large doses of imipramine and an MAO inhibitor in suicidal intent. JAMA 177:68-69, 1961 6. Lee F!: Imipramine overdosage-report of a fatal case. Br Med
Angeles Coun1934 Hospital
1-141
J, Luchins
1978
American
Psychiatric
Association
1411
CLINICAL
AND
RESEARCH
Am
REPORTS
J 1:338-339, 1961 7. Babiak W: Case fatality due to overdosage tranylcypromine (Parnate) and imipramine Assoc J 85:377, 1961
Social BY
DAVID
Adjustment L.
DUNNER,
in Primary M.D.,
8. Jarecki
of a combination (Tofranil). Can
Combined
amitriptyline
120:189, 1963 with other drugs.
November
and phenelzine Southern
1978
poisoning.
Med J 66:465-471,
J.
IGEL,
Disorder AND
RONALD
The purpose of this paper is to assess social adjustment in patients with primary affective disorder. Recently, Weissman and Paykel (1) studied social adjustment in depressed patients using a structured questionname-the Social Adjustment Scale-derived from an interview used by Gurland and associates (2). Their studies showed that the women dcprcssivcs had worse adjustment in several social areas when they were depressed than when euthymic, and that euthymic depressed patients showed worse social adjustment than controls. The population studied by Weissman and Paykel was described as having primarily unipolar depression. We have administered a self-report version of the Social Adjustment Scale (SAS-SR) to patients attending an outpatient lithium clinic (3). Our major interests were to describe the social adjustment states of these patients, most ofwhom had bipolar depression, and to compare data on the depressed women in our sample with the data reported by Weissman and Paykel. Method
R.
FIEVE,
M.D.
patient treatment for depression and hypomania. Patients were classified as unipolar if they had been hospitalizcd or treated for depression and had no history of mania or hypomania. All patients participated in the study voluntarily. Each patient was asked to complete the SAS-SR for the 2-week period preceding the clinic visit. This qucstionnaire consists of several questions in 6 areas of social adjustment (work, spare time, extended family, marital, parental, and family unit). The questions are each scored on a 5-point scale, with 1 representing cxcellcnt adjustment and S poorest adjustment. We obtamed mean scores for each area and for the questionnaire overall. Patients were instructed on filling out the questionnaire by one of us (G.I.), and the questionnaire was reviewed for completeness of response. At each clinic visit, the patient’s mood was assessed by a trained nurse or psychiatrist (6). Mood ratings were assessed independently of social adjustment data. Most ofthe patients in this study were treated on an open or double-blind basis with lithium carbonate. Results
The study was conducted in the lithium clinic of the New York State Psychiatric Institute. All 169 subjects met the diagnostic criteria of Fcighner and associates (4) for primary affective disorder and were further classified into bipolar and unipolar subtypes (5). Patients termed bipolar I had been hospitalized for mania at least once. Bipolar II patients had been hospitalized for depression only and had histories of hypomania. Patients termed ‘bipolar other’ had never been hospitalized for affective disorder but had received out‘
at the 28-Sept.
The authors are with the New York State West 168th St. , New York, N.Y. 10032, chiatrist, Mr. Igel is Research Assistant. Research, Lithium Clinic and Metabolic Associate Professor of Clinical Psychiatry, where Dr. Fieve is Professor of Clinical
VI World 3, 1977.
Congress
of
Psychiatric Institute, 722 where Dr. Dunner is Psyand Dr. Fieve is Chief of Unit. Dr. Dunner is also Columbia University, Psychiatry.
This work was supported in part by Alcohol, Drug Abuse, and Mental Health Administration grant MH-21586 from the National Institute of Mental Health and by the Foundation for Depression and Manic Depression.
0002-953X/78/OOl
1- 14 12$0.35
The breakdown of this sample by diagnosis and sex is presented in table 1 The overall mean adjustment scores for these patients did not differ significantly by diagnostic group or by sex. These overall means were about 2, indicating good but not optimum adjustment. The data were further analyzed by separating patients into cuthymic and noncuthymic groups. Most of the noneuthymic patients were mildly depressed, and noneuthymic patients had higher mean scores (worse adjustment) than euthymic patients in most areas of social adjustment. When patients were separated by median age, younger patients had worse adjustment in work, spare time, and extended family. No significant differences emerged when the data from our younger women were compared with the SAS-SR data from Weissman and Bothwell (7). Wcissman had evaluated the SAS-SR in a sample of up to 327 residents of the New Haven community (personal communication) and found that the mean values of the six social areas ranged from 1 .3 to 1 .9. Our 1 15 euthymic patients showed slightly higher mean scores, but these were within 1 standard deviation ofthe community controls. .
‘
Revised version of a paper presented Psychiatry, Honolulu, Hawaii, Aug.
1412
HG:
Am J Psychiatry 9. Ayd FJ: Doxepin
135:1/,
1973
Affective
GERARD
of Med
J Psychiatry
© 1978 American
Psychiatric
Association
J Psychiatry
Tricyclic BY
/35:/I,
November
Overdose
KERRIN
/978
CLINICAL
in a Patient
WHITE,
Given
Combined
Tricyclic-MAOI
RESEARCH
REPORTS
Treatment
M.D
ature was 98#{176}. He was described as being in stage 1 coma, i.e. , purposefully responsive to painful stimuli. His skin appeared flushed, especially over the lower extremities. Reflexes were normal. An ECG showed right bundle branch block. A complete blood count was normal except for dcvated white count (14,800), serum electrolytes were normal except for elevated uric acid (8.3), and serum liver function tests were normal except for elevated creatinine phosphokinase (810). The patient awoke the next day, depressed but otherwise without adverse after-effects and with no further abnormality.
Recent reviews have documented the safety of combining monoamine oxidase inhibitors (MAOIs) and tncyclic antidepressants, particularly if one avoids parenteral medications, use of imipramine, or the delayed addition of tnicyclics to established MAOI treatment (1-3). Reported overdoses have formed part of the ‘evidence’ against use of tricyclic-MAOI combinations (4-8). Reviewing fatal versus nonfatal overdoses involving both MAOIs and tricyclics, Ananth and Luchins (3) remarked, ‘In none of the non-fatal overdose cases was the patient on a course of MAOIs before taking the tricyclics. In this paper I will describe such a case, in part to offset the alarm evoked by earlien reports, since fear offatal reactions has prevented controlled research in this area for too long. ‘
AND
‘
‘
Discussion
‘ ‘
Case
This patient, tnicyclic-MAOI and presented
after more than a month of combined treatment overdosed on the tnicyclic a clinical picture consistent with typical tricyclic overdose. No hypertension, hyperthermia, or seizures occurred. This observation contrasts with the few catastrophic case reports of similar overdose situations, which have contributed to the bias against such combination therapy. It seems significant that the tncyclic overdose occurred in a patient already on the MAOI reputed to be most dangerous, tranylcypromine. On the other hand, this overdose involved doxepin, a drug not (to my knowledge) previously implicated in presumed adverse reactions to combination therapy. Although part of the explanation may be the more recent introduction ofdoxepin, this drug has certainly been combined with MAOIs before, as cvidenced by Ayd’s survey (9) of55 such cases, all apparently without untoward effect. Perhaps doxepin should supersede amitniptyline as a drug of choice for combination with MAOIs. Although this one case cannot prove that such combination therapy poses no special risks to patients who overdose, it is encouraging to those interested in combination therapy to know that one such overdose occurred without unusual consequences. Too often we pay attention to the rare disaster while losing sight of the less dramatic, more commonplace course of events.
Report
A 21-year-old man was admitted with the chief complaint of hearing the voice of a dead friend telling him to kill himself.
For
the
he had
been
received
one
previous
6 months,
intermittently
chlorpromazine
previous
and
psychiatric
fore this admission, sleeping and a 9. 1-kg
When
he was
admitted
after
the
depressed
death
and
amitriptyline
in day
hospitalization. he stopped weight loss,
A few
treatment, and began
he appeared
ofthis
suicidal
friend,
and care
weeks
had
and
in
be-
suffered fitful to hallucinate.
depressed,
hostile,
and
suicidal. Physician examination revealed no pathology other than obesity and chronic bronchitis. Complete blood count, serum electrolytes, and serum liver function tests were all essentially normal.
In part tyline,
because
he was
of his history
of poor
response
to amitrip-
started
on tranylcypromine, 10 mg q.a.m. , and doxepin, 50 mg q.h.s. ; gradually increased to tranylcypromine, 20 mg at 6:00 p.m. , and doxepin, 150 mg q.h.s. He complained mainly of drowsiness and dry mouth but also had a stiff neck (relieved by diazepam), nausea, and vomiting. Blood pressure, recorded daily, never rose above 140/ 100. After 17 days on this treatment, he began to improve, and 17 days later he was discharged with a 2-week supply of
both medications. Two days after scious. unknown memory
When
his discharge,
the police
found
him uncon-
He
had made a suicide attempt by overdosing on an quantity of doxepin. He later persistently denied of the events#{231}imrnediately preceding his overdose.
he was
first
examined
by paramedics,
his pulse
rate
REFERENCES
was I 10 per blood pressure stricted, with
minute, respiratory rate 40 per minute, and 1 14/80. His pupils were equal and conslow response to light and dysconjugate gaze. On admission to our medical unit, within 3 hours after the police found him, he was lavaged and pink capsules were recovered. Pulse rate was 1 10 and regular, respirations were 36 and regular, blood pressure was 130/72 and his temper-
1. Schuckit M, Robins E, Feighner J: Tricyclic antidepressants and monoamine oxidase inhibitors. Arch Gen Psychiatry 24:509-514, 1971 2. Spiker DG, Pugh DD: Combining tricyclic and monoamine oxidase inhibitor antidepressants. Arch Gen Psychiatry 33:828-. 830,
1976
3. Ananth therapy.
Dr. White is Assistant Professor of Psychiatry, ty-University of Southern California Medical Place, Los Angeles, Calif. 90033.
0002-953X/78/001
Los Center,
1$0.35
©
Compr
D: A review Psychiatry
ofcombined
18:221-230,
tricyclic
and MAOI
1977
4. Ayd FJ: Toxic somatic and psychopathologic reactions to antidepressant drugs. J Neuropsychiatry 2: 1 19-122, 1961 5. Luby ED, Domino EF: Toxicity from large doses of imipramine and an MAO inhibitor in suicidal intent. JAMA 177:68-69, 1961 6. Lee F!: Imipramine overdosage-report of a fatal case. Br Med
Angeles Coun1934 Hospital
1-141
J, Luchins
1978
American
Psychiatric
Association
1411
CLINICAL
AND
RESEARCH
Am
REPORTS
J 1:338-339, 1961 7. Babiak W: Case fatality due to overdosage tranylcypromine (Parnate) and imipramine Assoc J 85:377, 1961
Social BY
DAVID
Adjustment L.
DUNNER,
in Primary M.D.,
8. Jarecki
of a combination (Tofranil). Can
Combined
amitriptyline
120:189, 1963 with other drugs.
November
and phenelzine Southern
1978
poisoning.
Med J 66:465-471,
J.
IGEL,
Disorder AND
RONALD
The purpose of this paper is to assess social adjustment in patients with primary affective disorder. Recently, Weissman and Paykel (1) studied social adjustment in depressed patients using a structured questionname-the Social Adjustment Scale-derived from an interview used by Gurland and associates (2). Their studies showed that the women dcprcssivcs had worse adjustment in several social areas when they were depressed than when euthymic, and that euthymic depressed patients showed worse social adjustment than controls. The population studied by Weissman and Paykel was described as having primarily unipolar depression. We have administered a self-report version of the Social Adjustment Scale (SAS-SR) to patients attending an outpatient lithium clinic (3). Our major interests were to describe the social adjustment states of these patients, most ofwhom had bipolar depression, and to compare data on the depressed women in our sample with the data reported by Weissman and Paykel. Method
R.
FIEVE,
M.D.
patient treatment for depression and hypomania. Patients were classified as unipolar if they had been hospitalizcd or treated for depression and had no history of mania or hypomania. All patients participated in the study voluntarily. Each patient was asked to complete the SAS-SR for the 2-week period preceding the clinic visit. This qucstionnaire consists of several questions in 6 areas of social adjustment (work, spare time, extended family, marital, parental, and family unit). The questions are each scored on a 5-point scale, with 1 representing cxcellcnt adjustment and S poorest adjustment. We obtamed mean scores for each area and for the questionnaire overall. Patients were instructed on filling out the questionnaire by one of us (G.I.), and the questionnaire was reviewed for completeness of response. At each clinic visit, the patient’s mood was assessed by a trained nurse or psychiatrist (6). Mood ratings were assessed independently of social adjustment data. Most ofthe patients in this study were treated on an open or double-blind basis with lithium carbonate. Results
The study was conducted in the lithium clinic of the New York State Psychiatric Institute. All 169 subjects met the diagnostic criteria of Fcighner and associates (4) for primary affective disorder and were further classified into bipolar and unipolar subtypes (5). Patients termed bipolar I had been hospitalized for mania at least once. Bipolar II patients had been hospitalized for depression only and had histories of hypomania. Patients termed ‘bipolar other’ had never been hospitalized for affective disorder but had received out‘
at the 28-Sept.
The authors are with the New York State West 168th St. , New York, N.Y. 10032, chiatrist, Mr. Igel is Research Assistant. Research, Lithium Clinic and Metabolic Associate Professor of Clinical Psychiatry, where Dr. Fieve is Professor of Clinical
VI World 3, 1977.
Congress
of
Psychiatric Institute, 722 where Dr. Dunner is Psyand Dr. Fieve is Chief of Unit. Dr. Dunner is also Columbia University, Psychiatry.
This work was supported in part by Alcohol, Drug Abuse, and Mental Health Administration grant MH-21586 from the National Institute of Mental Health and by the Foundation for Depression and Manic Depression.
0002-953X/78/OOl
1- 14 12$0.35
The breakdown of this sample by diagnosis and sex is presented in table 1 The overall mean adjustment scores for these patients did not differ significantly by diagnostic group or by sex. These overall means were about 2, indicating good but not optimum adjustment. The data were further analyzed by separating patients into cuthymic and noncuthymic groups. Most of the noneuthymic patients were mildly depressed, and noneuthymic patients had higher mean scores (worse adjustment) than euthymic patients in most areas of social adjustment. When patients were separated by median age, younger patients had worse adjustment in work, spare time, and extended family. No significant differences emerged when the data from our younger women were compared with the SAS-SR data from Weissman and Bothwell (7). Wcissman had evaluated the SAS-SR in a sample of up to 327 residents of the New Haven community (personal communication) and found that the mean values of the six social areas ranged from 1 .3 to 1 .9. Our 1 15 euthymic patients showed slightly higher mean scores, but these were within 1 standard deviation ofthe community controls. .
‘
Revised version of a paper presented Psychiatry, Honolulu, Hawaii, Aug.
1412
HG:
Am J Psychiatry 9. Ayd FJ: Doxepin
135:1/,
1973
Affective
GERARD
of Med
J Psychiatry
© 1978 American
Psychiatric
Association
