LETTERS TO THE EDITOR
which side-effects become problematic, particularly tremor and cognitive impairment. Although lithium is the treatment of choice for bipolar disorder, there is a significant percentage of patients (20% to 30%) who do not respond to or tolerate lithium (4). There is evidence that carbamazepine is efficacious in the acute and prophylactic treatment of bipolar disorder but there is less evidence of the efficacy of valproic acid (1). Randomized controlled trials comparing valproic acid and lithium and/or the combination are needed in bipolar disorder and the rapid cycling subtype in particular.
CLINICAL EXPERIENCE WITH VALPROIC ACID IN 22 PATIENTS WITH REFRACTORY BIPOLAR MOOD DISORDER Dear Sir: We have followed with great interest reports on the efficacy of valproic acid in patients with bipolar disorder refractory to lithium or carbamazepine (1-3). Most reports suggest that although valproic acid shows promise, it requires further study. There is little mention of adverse reactions. Our experience with valproic acid in 22 patients with highly refractory bipolar disorder reveals a spectrum of efficacy consistent with other reports in the literature (3).
References 1. Small JG. Anticonvulsants in affective disorders. Psy-
Twenty of these patients were female, two were male. Their mean age was 47 years ± 15 years, with a range from 24 to 70 years. Eleven patients had bipolar I disorder, ten had bipolar I disorder with a rapid cycling course, and one had bipolar II disorder. At our initial observation, the mean duration of therapy was 7 ± 2.7 months, with a range of three to 12 months. Mean dosage of valproic acid was 1,400 mg ± 750 mg, with a range of 500 mg to 3,000 mg. Only two patients received monotherapy with valproic acid. The remaining patients were receiving either lithium, carbamazepine, antipsychotics, thyroid supplementation or a combination of these.
chopharmacol Bull 1990; 26(1). 2. Post RM. Introduction: emerging perspectives on valproate in affective disorders. J Clin Psychiatry 1989; 50(3 Suppl). 3. Calabrese JR, Delucchi GA. Spectrum of efficacy of valproate in 55 patients with rapid-cycling bipolar disorder. Am J Psychiatry 1990; 147(4). 4. Goodwin FK, Jamison K. Manic-depressive illness. New York: Oxford University Press, 1990. R. Guscott, M.D. Hamilton, Ontario
Nine of 22 patients showed a marked response to the mood stabilizing properties of valproic acid based on clinicians' global judgement. Five of these patients suffered from rapid cycling disorder. This finding is consistent with the suggestion in the literature that valproic acid may be of some specific benefit in rapid cycling disorder (3).
INTERACTION OF FLUOXETINE AND CHLORAL HYDRATE Dear Sir: I wish to report the case of a patient being treated with fluoxetine who developed moderate but prolonged drowsiness when concurrently taking chloral hydrate. It is my belief that this is the first report to document this side-effect resulting form the interaction offluoxetine and chloral hydrate. Ms. D, a 42 year old women with a recurrent depressive disorder was started on 20 mg of fluoxetine daily. The standard tricyclic antidepressants had previously been tried, and she had responded in varying degrees to them. Her compliance to tricyclics was poor, and she correctly related this to the troublesome side-effects, especially sedation. Approximately ten days after starting on fluoxetine, Ms. D was given 500 mg of chloral hydrate since she was complaining of worsening insomnia. The following morning she appeared drowsy and stayed in bed. A neurological work up was unremarkable. Fluoxetine and chloral hydrate were discontinued; she was not taking any other medications. There were no other probable reasons for her drowsiness. She continued to remain drowsy until the next day, when the drowsiness gradually started to wear off. Chloral hydrate was tried again on a later day, and she was able to tolerate up to 1,000 mg with no adverse consequences. After oral administration of 500 mg of chloral hydrate, the mild cerebral depressant effect of chloral hydrate and its metabolite trichloroethanollasts up to eight hours (1). The chloral hydrate and trichloroethanol eventually oxidize in the liver into trichloroacetic and are excreted in the urine (2). Fluoxetine is known to interfere with the hepatic metabolism of several drugs, including tricyclic
At the second observation, six months after our initial observations, six of the nine patients who responded to the medication continued to show a favourable response; they were evenly divided between those with bipolar I disorder and those with the rapid cycling subtype. Two of the three patients who were no longer on valproic acid relapsed into a rapid cycling course; one had Parkinson's disease and the other was intermittently non compliant. The third patient relapsed but responded to further treatment with carbamazepine and lithium only. Our open uncontrolled study is clearly biased against establishing the efficacy of valproic acid's mood stabilizing properties, given the highly selected and refractory nature of our patients. Our clinic provides service to those patients unresponsive to multiple trials of other mood stabilizing agents, thus limiting the extent to which our results can be generalized. Although the literature suggests that valproic acid is generally well-tolerated by patients, we observed that patients complained of tremor, diarrhea, urinary urgency and cognitive impairment in the higher dose range (Le., > 1,500 mg per day). Significant alopecia was noticed in three patients. However, only two patients received monotherapy with valproic acid and neither suffered from side-effects (both were also non responders). Our own uncontrolled observations suggest that 1,500 mg per day is the cut-off dose beyond 590
October, 1992
LETTERS TO THE EDITOR
antidepressants (3) and diazepam (4). Therefore, it is conceivable that in this case fluoxetine interfered with the metabolic degradation of chloral hydrate. It is also likely that fluoxetine, which has a high affinity to carrier protein, displaced chloral hydrate from its binding sites, causing an enhanced and prolonged drowsiness. Insomnia is the third most commonly reported side-effect of fluoxetine, and chloral hydrate is one of the safest and most commonly used hypnotic sedatives. However, the potential interaction between these two drugs should be kept in mind when they are administered together.
References I. AHFS Drug Information. Bethesda MD: American Society of Hospital Pharmacists, 1990; 28: 24. 2. AHFS Drug Information. Bethesda MD: American Society of Hospital Pharmacists, 1990; 28: 92. 3. Downs 1M, et al. Increased plasma tricyclic concentration in two patient concurrently treated with fluoxetine. J Clin Psychiatry 1989; 50: 226-227. 4. Lemberger L, Rowe i-J, et al. The effect of fluoxetine in the pharmacokinetics and psychomotor response of diazepam. Clin Pharmacol Ther 1988; 43: 412-419. S. Devarajan, M.B.,B.S. Halifax, Nova Scotia WHAT IS BEHAVIOUR THERAPY? Dear Sir: It was with great interest we read the recent article by Dr. Camenietzki (I), particularly because we believe there is insufficient information on the clinical applications of behavioural (and cognitive) techniques in the mainstream psychiatric literature. In our opinion, much of the literature over the past decade on the efficacy and detailed protocol of cognitive-behavioural therapy for the anxiety disorders has not reached the general psychiatric readership. This point is apparent in Dr. Camenietzki's admission offrustration with psychotherapy for anxiety patients over the past II years. Although we admire Dr. Camenietzki's openness in exploring behavioural techniques, we believe there are several errors in this paper which necessitate correction. Dr. Camenietzki claims relaxation training and desensitization are effective for some phobias and cites a paper on desensitization that is almost 20 years old. Recent research literature clearly indicates that in vivo exposure is superior to these types of treatments for phobic states, including agoraphobia (2,3).. Dr. Camenietzki does not recommend behaviour therapy for social phobia and instead emphasizes group psychotherapy. He does not consider cognitive-behavioural therapy for social phobia on a group basis, a procedure which has demonstrated efficacy (4,5). It should also be noted that many patients make valuable "insights" during in vivo exposure sessions and the two are not always mutually exclusive. Dr. Camenietzki talks of exposure and flooding as if they were the same techniques. In fact, in vivo exposure is not necessarily flooding. Rather than "bombarding the patient with images of pain, fear and suffering" (i.e., implosion), it is more useful for the patient to confront feared situations and symptoms in vivo, in a gradual way, according to targets that the patient sets (2,3,6,7). This approach may also result in less of the "clinical bargaining" and "fussing" that Dr. Camenietzki describes. The breathing control and correction of cognitive distortions that
591
Dr. Camenietzki mentions are important components of successful therapy. However, one of the most effective cognitive-behavioural techniques for controlling anxiety involves exposing the patient to feared symptoms through such means as voluntary hyperventilation in order to reinterpret feared bodily sensations (6). This approach appears to be far more promising than desensitization for treating anxiety but is not mentioned in Dr. Camenietzki's paper. Dr. Camenietzki believes it is important to engage in clinical bargaining with the patient by making increasing demands, and claims it is essential to "fuss" over the smallest details. He cites a case where he spent 40 minutes fussing with a patient on how she would spend the first 30 seconds in a feared shopping mall. The 40 minutes may have been better spent conducting therapist-aided in vivo exposure at the particular shopping mall. In behaviour therapy the patient, rather than the therapist, should be setting goals. Further, the real goal of exposure is not to see how many subway stops a patient can travel, but to remain in the feared situation or as near to it as possible until the anxiety decreases (rather than "white knuckling" it for a short time). We also find Dr. Camenietzki's frequent analogies to the motherchild relationship to be very condescending towards the patient and may in fact foster dependence. Similarly, we also find it condescending to describe the behaviour therapist as concerned only with "graphs and diaries" while the psychotherapist maintains a "face-toface dialogue." We agree with Dr. Camenietzki's assertion that different clinical skills are emphasized in the two approaches, but despite his protestations otherwise, he has combined the roles of psychotherapist and behaviour therapist in his article (the description of fussing is a good example). This leads to confusion for the reader. A final point concerns the rationale of therapy provided to the patient. We believe the patient should always be informed that the most integral part of treatment and determinant of improvement is the regular homework of in vivo exposure. Dr. Camenietzki only reports doing this "in the heat of countertransference." Behaviour therapy has been shown to reduce the excessive health care utilization by anxiety disorder patients (8). There is a great need in the general psychiatric literature for authoritative advice from authors such as Barlow (2) and Marks (3), not an idiosyncratic paper that belittles behaviour therapy. It is unlikely that an article entitled, "A Behaviour Therapist Engages in Pharmacotherapy" (or psychoanalysis for that matter) would appear in a refereed psychiatric journal. Cognitive-behaviour therapy is not a clinical skill that can just be "picked up" along the way of clinical practice.
1.
2. 3. 4. 5. 6.
References Camenietzki S. A psychotherapist engages in behaviour therapy. Can J Psychiatry 1991; 36(7): 492-496. Barlow DH. Anxiety and its disorders: the nature and treatment of anxiety and panic. New York: Guilford Press, 1988. Marks 1M. Fears, phobias and rituals. Oxford: Oxford University Press, 1987. Mattick Rp, Peters L, Clarke Je. Exposure and cognitive restructuring for social phobia: A controlled study. Behavior Therapy 1989; 20: 3-23. Butler G. Issues in the application of cognitive and behavioral strategies to the treatment of social phobia. Clinical Psychology Review 1989; 9: 91-106. Walker JR, Norton GR, Ross CA. Panic disorder and agoraphobia: a comprehensive guide for the practitioner. Pacific Grove CA: Brooks/Cole, 1990.
which side-effects become problematic, particularly tremor and cognitive impairment. Although lithium is the treatment of choice for bipolar disorder, there is a significant percentage of patients (20% to 30%) who do not respond to or tolerate lithium (4). There is evidence that carbamazepine is efficacious in the acute and prophylactic treatment of bipolar disorder but there is less evidence of the efficacy of valproic acid (1). Randomized controlled trials comparing valproic acid and lithium and/or the combination are needed in bipolar disorder and the rapid cycling subtype in particular.
CLINICAL EXPERIENCE WITH VALPROIC ACID IN 22 PATIENTS WITH REFRACTORY BIPOLAR MOOD DISORDER Dear Sir: We have followed with great interest reports on the efficacy of valproic acid in patients with bipolar disorder refractory to lithium or carbamazepine (1-3). Most reports suggest that although valproic acid shows promise, it requires further study. There is little mention of adverse reactions. Our experience with valproic acid in 22 patients with highly refractory bipolar disorder reveals a spectrum of efficacy consistent with other reports in the literature (3).
References 1. Small JG. Anticonvulsants in affective disorders. Psy-
Twenty of these patients were female, two were male. Their mean age was 47 years ± 15 years, with a range from 24 to 70 years. Eleven patients had bipolar I disorder, ten had bipolar I disorder with a rapid cycling course, and one had bipolar II disorder. At our initial observation, the mean duration of therapy was 7 ± 2.7 months, with a range of three to 12 months. Mean dosage of valproic acid was 1,400 mg ± 750 mg, with a range of 500 mg to 3,000 mg. Only two patients received monotherapy with valproic acid. The remaining patients were receiving either lithium, carbamazepine, antipsychotics, thyroid supplementation or a combination of these.
chopharmacol Bull 1990; 26(1). 2. Post RM. Introduction: emerging perspectives on valproate in affective disorders. J Clin Psychiatry 1989; 50(3 Suppl). 3. Calabrese JR, Delucchi GA. Spectrum of efficacy of valproate in 55 patients with rapid-cycling bipolar disorder. Am J Psychiatry 1990; 147(4). 4. Goodwin FK, Jamison K. Manic-depressive illness. New York: Oxford University Press, 1990. R. Guscott, M.D. Hamilton, Ontario
Nine of 22 patients showed a marked response to the mood stabilizing properties of valproic acid based on clinicians' global judgement. Five of these patients suffered from rapid cycling disorder. This finding is consistent with the suggestion in the literature that valproic acid may be of some specific benefit in rapid cycling disorder (3).
INTERACTION OF FLUOXETINE AND CHLORAL HYDRATE Dear Sir: I wish to report the case of a patient being treated with fluoxetine who developed moderate but prolonged drowsiness when concurrently taking chloral hydrate. It is my belief that this is the first report to document this side-effect resulting form the interaction offluoxetine and chloral hydrate. Ms. D, a 42 year old women with a recurrent depressive disorder was started on 20 mg of fluoxetine daily. The standard tricyclic antidepressants had previously been tried, and she had responded in varying degrees to them. Her compliance to tricyclics was poor, and she correctly related this to the troublesome side-effects, especially sedation. Approximately ten days after starting on fluoxetine, Ms. D was given 500 mg of chloral hydrate since she was complaining of worsening insomnia. The following morning she appeared drowsy and stayed in bed. A neurological work up was unremarkable. Fluoxetine and chloral hydrate were discontinued; she was not taking any other medications. There were no other probable reasons for her drowsiness. She continued to remain drowsy until the next day, when the drowsiness gradually started to wear off. Chloral hydrate was tried again on a later day, and she was able to tolerate up to 1,000 mg with no adverse consequences. After oral administration of 500 mg of chloral hydrate, the mild cerebral depressant effect of chloral hydrate and its metabolite trichloroethanollasts up to eight hours (1). The chloral hydrate and trichloroethanol eventually oxidize in the liver into trichloroacetic and are excreted in the urine (2). Fluoxetine is known to interfere with the hepatic metabolism of several drugs, including tricyclic
At the second observation, six months after our initial observations, six of the nine patients who responded to the medication continued to show a favourable response; they were evenly divided between those with bipolar I disorder and those with the rapid cycling subtype. Two of the three patients who were no longer on valproic acid relapsed into a rapid cycling course; one had Parkinson's disease and the other was intermittently non compliant. The third patient relapsed but responded to further treatment with carbamazepine and lithium only. Our open uncontrolled study is clearly biased against establishing the efficacy of valproic acid's mood stabilizing properties, given the highly selected and refractory nature of our patients. Our clinic provides service to those patients unresponsive to multiple trials of other mood stabilizing agents, thus limiting the extent to which our results can be generalized. Although the literature suggests that valproic acid is generally well-tolerated by patients, we observed that patients complained of tremor, diarrhea, urinary urgency and cognitive impairment in the higher dose range (Le., > 1,500 mg per day). Significant alopecia was noticed in three patients. However, only two patients received monotherapy with valproic acid and neither suffered from side-effects (both were also non responders). Our own uncontrolled observations suggest that 1,500 mg per day is the cut-off dose beyond 590
October, 1992
LETTERS TO THE EDITOR
antidepressants (3) and diazepam (4). Therefore, it is conceivable that in this case fluoxetine interfered with the metabolic degradation of chloral hydrate. It is also likely that fluoxetine, which has a high affinity to carrier protein, displaced chloral hydrate from its binding sites, causing an enhanced and prolonged drowsiness. Insomnia is the third most commonly reported side-effect of fluoxetine, and chloral hydrate is one of the safest and most commonly used hypnotic sedatives. However, the potential interaction between these two drugs should be kept in mind when they are administered together.
References I. AHFS Drug Information. Bethesda MD: American Society of Hospital Pharmacists, 1990; 28: 24. 2. AHFS Drug Information. Bethesda MD: American Society of Hospital Pharmacists, 1990; 28: 92. 3. Downs 1M, et al. Increased plasma tricyclic concentration in two patient concurrently treated with fluoxetine. J Clin Psychiatry 1989; 50: 226-227. 4. Lemberger L, Rowe i-J, et al. The effect of fluoxetine in the pharmacokinetics and psychomotor response of diazepam. Clin Pharmacol Ther 1988; 43: 412-419. S. Devarajan, M.B.,B.S. Halifax, Nova Scotia WHAT IS BEHAVIOUR THERAPY? Dear Sir: It was with great interest we read the recent article by Dr. Camenietzki (I), particularly because we believe there is insufficient information on the clinical applications of behavioural (and cognitive) techniques in the mainstream psychiatric literature. In our opinion, much of the literature over the past decade on the efficacy and detailed protocol of cognitive-behavioural therapy for the anxiety disorders has not reached the general psychiatric readership. This point is apparent in Dr. Camenietzki's admission offrustration with psychotherapy for anxiety patients over the past II years. Although we admire Dr. Camenietzki's openness in exploring behavioural techniques, we believe there are several errors in this paper which necessitate correction. Dr. Camenietzki claims relaxation training and desensitization are effective for some phobias and cites a paper on desensitization that is almost 20 years old. Recent research literature clearly indicates that in vivo exposure is superior to these types of treatments for phobic states, including agoraphobia (2,3).. Dr. Camenietzki does not recommend behaviour therapy for social phobia and instead emphasizes group psychotherapy. He does not consider cognitive-behavioural therapy for social phobia on a group basis, a procedure which has demonstrated efficacy (4,5). It should also be noted that many patients make valuable "insights" during in vivo exposure sessions and the two are not always mutually exclusive. Dr. Camenietzki talks of exposure and flooding as if they were the same techniques. In fact, in vivo exposure is not necessarily flooding. Rather than "bombarding the patient with images of pain, fear and suffering" (i.e., implosion), it is more useful for the patient to confront feared situations and symptoms in vivo, in a gradual way, according to targets that the patient sets (2,3,6,7). This approach may also result in less of the "clinical bargaining" and "fussing" that Dr. Camenietzki describes. The breathing control and correction of cognitive distortions that
591
Dr. Camenietzki mentions are important components of successful therapy. However, one of the most effective cognitive-behavioural techniques for controlling anxiety involves exposing the patient to feared symptoms through such means as voluntary hyperventilation in order to reinterpret feared bodily sensations (6). This approach appears to be far more promising than desensitization for treating anxiety but is not mentioned in Dr. Camenietzki's paper. Dr. Camenietzki believes it is important to engage in clinical bargaining with the patient by making increasing demands, and claims it is essential to "fuss" over the smallest details. He cites a case where he spent 40 minutes fussing with a patient on how she would spend the first 30 seconds in a feared shopping mall. The 40 minutes may have been better spent conducting therapist-aided in vivo exposure at the particular shopping mall. In behaviour therapy the patient, rather than the therapist, should be setting goals. Further, the real goal of exposure is not to see how many subway stops a patient can travel, but to remain in the feared situation or as near to it as possible until the anxiety decreases (rather than "white knuckling" it for a short time). We also find Dr. Camenietzki's frequent analogies to the motherchild relationship to be very condescending towards the patient and may in fact foster dependence. Similarly, we also find it condescending to describe the behaviour therapist as concerned only with "graphs and diaries" while the psychotherapist maintains a "face-toface dialogue." We agree with Dr. Camenietzki's assertion that different clinical skills are emphasized in the two approaches, but despite his protestations otherwise, he has combined the roles of psychotherapist and behaviour therapist in his article (the description of fussing is a good example). This leads to confusion for the reader. A final point concerns the rationale of therapy provided to the patient. We believe the patient should always be informed that the most integral part of treatment and determinant of improvement is the regular homework of in vivo exposure. Dr. Camenietzki only reports doing this "in the heat of countertransference." Behaviour therapy has been shown to reduce the excessive health care utilization by anxiety disorder patients (8). There is a great need in the general psychiatric literature for authoritative advice from authors such as Barlow (2) and Marks (3), not an idiosyncratic paper that belittles behaviour therapy. It is unlikely that an article entitled, "A Behaviour Therapist Engages in Pharmacotherapy" (or psychoanalysis for that matter) would appear in a refereed psychiatric journal. Cognitive-behaviour therapy is not a clinical skill that can just be "picked up" along the way of clinical practice.
1.
2. 3. 4. 5. 6.
References Camenietzki S. A psychotherapist engages in behaviour therapy. Can J Psychiatry 1991; 36(7): 492-496. Barlow DH. Anxiety and its disorders: the nature and treatment of anxiety and panic. New York: Guilford Press, 1988. Marks 1M. Fears, phobias and rituals. Oxford: Oxford University Press, 1987. Mattick Rp, Peters L, Clarke Je. Exposure and cognitive restructuring for social phobia: A controlled study. Behavior Therapy 1989; 20: 3-23. Butler G. Issues in the application of cognitive and behavioral strategies to the treatment of social phobia. Clinical Psychology Review 1989; 9: 91-106. Walker JR, Norton GR, Ross CA. Panic disorder and agoraphobia: a comprehensive guide for the practitioner. Pacific Grove CA: Brooks/Cole, 1990.
