June, 1991
LETfEllS TO THE EDITOR
tions often involve a reworking of daytime material in the sense of floating and loss of balance, while hypnopomic ones have more intense, dream-like quality (1). Sleep epilepsy related to organic lesion in 25% of cases can occur in both REM and non REM sleep or on arousal, either as generalized or partial seizures; these occur most frequently during the first two hours of sleep or between 4:00 and 6:00 a.m. (I). Psychomotor attacks appear most often in REM sleep and the interictal EEO. Boller et al (2) reported the case of a man with repeated episodes of fearful awakening from sleep often with "frightful visions," as well as some that occurred during the day; a typical episode showed a slow wave focus over the right parietotemporal area during stage 2 to 3 sleep, introducing 20 seconds of awakening while the patient remained behaviourally asleep. The CAT scan demonstrated a right temporal lobe infarction. The symptoms were relieved with dephenylhydantoin. The phenomena in this patient resembled hypnopomic hallucinations, but manipulation of the tricyclic antidepressant did not provide relief. Although the lesions are not in the areas affecting visual pathways or sleep mechanisms, it seems clear that they gave rise to abnormal discharges, and treatment with anticonvulsants resulted in control.
References
I. Parks, JD. Sleep and its disorders. London: W.B. Saunders, 1985. 2. Boller F, Wright DO, Cavalieri R, et al. Paroxysmal "nightmares": sequel of a stroke responsive to diphenylhydantoin. Neurology 1975; 25: 1026-1028. Stephen Fortus Signer, M.D. Michael Krelina, M.D. San Diego, California
FLUSHING REACTION ASSOCIATED WITHTHE INTERACTION OF PHENELZINE AND CLONAZEPAM
Dear Sir: There has been one report in the literature of an interaction between phenelzine and clonazepam associated with a flushing reaction (I). We wish to report a second case. The patient is a 39-year-old single woman who was started on phenelzine for treatment of dysthymic disorder associated with panic attacks and generalized anxiety. This followed a 16 day washout period, prior to which she had been taking trimipramine 25 mg tid and 125 mg hs, Medications on admission included ranitidine 300 mg hs, acetaminophen 650 mg q 6 h pm, salbutamol inhaler 2 puffs q 4 h while awake and clonazeparn 2 mg qid. Routine investigations were normal. Blood pressures tid were normal. After one week, salbutamol was discontinued and phenelzine 15 mg once daily was started, Phenelzine was gradually increased to 15 mg qid; occasional doses were withheld because of mild hypotension. When the phenelzine dose was 15 mg tid, the patient began to complain of facial flushing in the mid-afternoon just once per day. Because her anxiety was improving and she was becoming drowsy, clonazepam was gradually decreased by I mg. This resulted in improvement of the flushing, which did not worsen when phenelzine was increased. She had no further flushing when clonazepam was reduced to I mg tid and 2 mg hs, about 13 days after the flushing began. Clonazepam was decreased further to 0.5 mg tid and I mg hs with no further difficulties, while phenelzine remained at 15 mg qid. During this time, she had occasional mild headaches, occurring at
389
most once per day, which were relieved by acetaminophen. She did not have any hypertensive episodes, and the headaches were not associated with the flushing. Eppel (I) has already speculated on the basis for this interaction. Although we are unable to offer any new insight, we hope that this second report will help make clinicians more aware of this potentially serious interaction.
References I. Eppel A. Interaction between clonazepam and phenelzine. Can J Psychiatry 1990; 35(7): 647. James L. Karagianis, M.D. Hilary March, M.D. St. John Newfoundland
s,
LATEONSET (HYPO)MANIA
Dear Sir: Dr. Lucie Fortin's recent review of the literature on mania in the elderly (I) reflects the rarity of this striking clinical condition in general. Manic or hypomanic episodes were identified in only 0.85% of psychiatric outpatients (2), and 0.6% of admissions of elderly patients to hospital were due to mania (3). The onset of the manic presentations of mood disorder, which traditionally occur between the late 20s and early 30s (I). However, in one survey it was found to occur on the average about a decade later (2); the range of age of onset was between 15 and 63 years. Such a delay of manic debuts may well reflect increasing life-expectancy. As noted also by Sir Martin Roth (3), there are epidemiological differences between the genders. While only about 30% of men first presented with mania at age 45 or later, close to one-half of women were debuting in this age bracket (2). This might be due to the differences in the average life-expectancy between men and women. Interestingly, the manic debuts of bipolar mood disorder were more common among men (almost 70% versus approximately 40% in women), as was "unipolar mania" (about twice as common in men than women). Most cases of mania in the studies reviewed by Dr. Fortin occurred after a few depressive episodes. Whereas clinical depression afflicts women more often, men may be susceptible to primary mania as they are to hyperactivity/attention deficit disorder or enuresis (4). Secondary mania, or manic presentations of organic mood disorder, are more common in women. An astounding variety of medicosurgical pathology was found in over 60% of women and only half as many men. Confusion or other indices of "organicity" were identified in two-thirds of women with (hypo)mania, and less than one-half of men, regardless of age (2). As with any refutation of facts or hypotheses, ruling out an underlying organic brain disorder is less reliable than settling for the diagnosis of secondary mania. The prevailing diagnostic approach leaves much room for arbitrariness in this regard (5). The feeble exclusion criterion (F) for a primary (manic) mood disorder is enunciated as a double negative: "it cannot be established that an organic factor initiated and maintained [it]" (I). Organic mental disorders associated with axis III physical disorders or conditions (i.e., organic mood disorder) presumably represent at least co-morbidity, ifnot an etiological link, but the alternative of unknown etiology weakens such a presumption (5). The arbitrariness is explicitly condoned in the statement that an organic mood disorder be supported by "evidence from the history, physical exam-
LETfEllS TO THE EDITOR
tions often involve a reworking of daytime material in the sense of floating and loss of balance, while hypnopomic ones have more intense, dream-like quality (1). Sleep epilepsy related to organic lesion in 25% of cases can occur in both REM and non REM sleep or on arousal, either as generalized or partial seizures; these occur most frequently during the first two hours of sleep or between 4:00 and 6:00 a.m. (I). Psychomotor attacks appear most often in REM sleep and the interictal EEO. Boller et al (2) reported the case of a man with repeated episodes of fearful awakening from sleep often with "frightful visions," as well as some that occurred during the day; a typical episode showed a slow wave focus over the right parietotemporal area during stage 2 to 3 sleep, introducing 20 seconds of awakening while the patient remained behaviourally asleep. The CAT scan demonstrated a right temporal lobe infarction. The symptoms were relieved with dephenylhydantoin. The phenomena in this patient resembled hypnopomic hallucinations, but manipulation of the tricyclic antidepressant did not provide relief. Although the lesions are not in the areas affecting visual pathways or sleep mechanisms, it seems clear that they gave rise to abnormal discharges, and treatment with anticonvulsants resulted in control.
References
I. Parks, JD. Sleep and its disorders. London: W.B. Saunders, 1985. 2. Boller F, Wright DO, Cavalieri R, et al. Paroxysmal "nightmares": sequel of a stroke responsive to diphenylhydantoin. Neurology 1975; 25: 1026-1028. Stephen Fortus Signer, M.D. Michael Krelina, M.D. San Diego, California
FLUSHING REACTION ASSOCIATED WITHTHE INTERACTION OF PHENELZINE AND CLONAZEPAM
Dear Sir: There has been one report in the literature of an interaction between phenelzine and clonazepam associated with a flushing reaction (I). We wish to report a second case. The patient is a 39-year-old single woman who was started on phenelzine for treatment of dysthymic disorder associated with panic attacks and generalized anxiety. This followed a 16 day washout period, prior to which she had been taking trimipramine 25 mg tid and 125 mg hs, Medications on admission included ranitidine 300 mg hs, acetaminophen 650 mg q 6 h pm, salbutamol inhaler 2 puffs q 4 h while awake and clonazeparn 2 mg qid. Routine investigations were normal. Blood pressures tid were normal. After one week, salbutamol was discontinued and phenelzine 15 mg once daily was started, Phenelzine was gradually increased to 15 mg qid; occasional doses were withheld because of mild hypotension. When the phenelzine dose was 15 mg tid, the patient began to complain of facial flushing in the mid-afternoon just once per day. Because her anxiety was improving and she was becoming drowsy, clonazepam was gradually decreased by I mg. This resulted in improvement of the flushing, which did not worsen when phenelzine was increased. She had no further flushing when clonazepam was reduced to I mg tid and 2 mg hs, about 13 days after the flushing began. Clonazepam was decreased further to 0.5 mg tid and I mg hs with no further difficulties, while phenelzine remained at 15 mg qid. During this time, she had occasional mild headaches, occurring at
389
most once per day, which were relieved by acetaminophen. She did not have any hypertensive episodes, and the headaches were not associated with the flushing. Eppel (I) has already speculated on the basis for this interaction. Although we are unable to offer any new insight, we hope that this second report will help make clinicians more aware of this potentially serious interaction.
References I. Eppel A. Interaction between clonazepam and phenelzine. Can J Psychiatry 1990; 35(7): 647. James L. Karagianis, M.D. Hilary March, M.D. St. John Newfoundland
s,
LATEONSET (HYPO)MANIA
Dear Sir: Dr. Lucie Fortin's recent review of the literature on mania in the elderly (I) reflects the rarity of this striking clinical condition in general. Manic or hypomanic episodes were identified in only 0.85% of psychiatric outpatients (2), and 0.6% of admissions of elderly patients to hospital were due to mania (3). The onset of the manic presentations of mood disorder, which traditionally occur between the late 20s and early 30s (I). However, in one survey it was found to occur on the average about a decade later (2); the range of age of onset was between 15 and 63 years. Such a delay of manic debuts may well reflect increasing life-expectancy. As noted also by Sir Martin Roth (3), there are epidemiological differences between the genders. While only about 30% of men first presented with mania at age 45 or later, close to one-half of women were debuting in this age bracket (2). This might be due to the differences in the average life-expectancy between men and women. Interestingly, the manic debuts of bipolar mood disorder were more common among men (almost 70% versus approximately 40% in women), as was "unipolar mania" (about twice as common in men than women). Most cases of mania in the studies reviewed by Dr. Fortin occurred after a few depressive episodes. Whereas clinical depression afflicts women more often, men may be susceptible to primary mania as they are to hyperactivity/attention deficit disorder or enuresis (4). Secondary mania, or manic presentations of organic mood disorder, are more common in women. An astounding variety of medicosurgical pathology was found in over 60% of women and only half as many men. Confusion or other indices of "organicity" were identified in two-thirds of women with (hypo)mania, and less than one-half of men, regardless of age (2). As with any refutation of facts or hypotheses, ruling out an underlying organic brain disorder is less reliable than settling for the diagnosis of secondary mania. The prevailing diagnostic approach leaves much room for arbitrariness in this regard (5). The feeble exclusion criterion (F) for a primary (manic) mood disorder is enunciated as a double negative: "it cannot be established that an organic factor initiated and maintained [it]" (I). Organic mental disorders associated with axis III physical disorders or conditions (i.e., organic mood disorder) presumably represent at least co-morbidity, ifnot an etiological link, but the alternative of unknown etiology weakens such a presumption (5). The arbitrariness is explicitly condoned in the statement that an organic mood disorder be supported by "evidence from the history, physical exam-
