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AM. J. DRUG ALCOHOL ABUSE, 18(1), pp. 57-62 (1992)
Cocaine-Associated Panic Attacks in Methadone-Maintained Patients Marc I. Rosen,* MD Department of Psychiatry Yale University New Haven, Connecticut 0651 1
Thomas Kosten, MD Substance Abuse Treatment Unit Department of Psychiatry Yale University New Haven, Connecticut 06519
ABSTRACT The incidence of panic attacks methadone-maintained patients has increased over a 10-year period from 1 to 6-13%. Cocaine use appears to be associated with this increase, although other environmental and constitutional factors may be contributory. Patients with cocaineassociated panic differ from other panic patients in rates of psychiatric hospitalization and medical illness, but not in depression, other drug use, or agoraphobia.
INTRODUCTION Cocaine has been noted in several recent reports to precipitate panic disorder in patients who had not previously suffered from panic attacks [ 1, 21. We have noticed more panic patients in the Yale Methadone Maintenance Clinics during the last 10 years, and studied whether cocaine was responsible. We also examined
*To whom requests for reprints should be addressed at Substance Abuse Treatment Unit, 27 Sylvan Avenue, New Haven, Connecticut 0651 1. Telephone: (203) 785-2154.
57
ROSEN AND KOSTEN
58
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
whether other comorbidity was more common among those patients whose panic attacks were precipitated by cocaine than among other panic patients.
METHOD The 280 patients in the long-term Yale Methadone Maintenance Program (stays range from 2 to 15 years) were screened by using a brief questionnaire asking whether the patient had ever had an anxiety attack, had three attacks in a 3-week period, or been treated for anxiety. Sixty-six of the 141 respondents answered yes to two of the three questions. These patients were then interviewed in more detail by using the Structured Clinical Interview for DSM-III-R (SCID) by M.R. to see if they satisfied DSM-111-R criteria for panic attacks. The 18 clients who met DSM-111-R criteria for panic attacks were then asked about other substance use, whether other substance use preceeded the onset of frequent (more than Wmonth) panic attacks, hospitalization for psychiatric reasons, episodes of depression with neurovegetative symptoms, and whether others in their immediate families suffered from psychiatric disorders, including substance abuse, suicide, depression, and panic attacks. The patients’ twice monthly urine toxicology screens were reviewed to verify if recent sustance abuse had occurred. These results were compared with the incidences of panic disorder found in 1978 during a similar screening of 120 patients at the Yale Methadone Program [3].
RESULTS The most conservative prevalence of panic disorder is 6% (18/280), although among the 141 respondents the rate is 13% (n = 18) and the rate of self-reporting two out of three key panic symptoms is 46% (66/141). All of the 18 patients had used cocaine at some time in the past. Nine patients had at some time been “heavy” cocaine users (eight with several month periods of intravenous use; one who had free-based for several months). The other nine patients had used cocaine fewer than 10 times in their lives; these “experimenters” all denied cocaine use within the past year. Table 1 compares the nine patients with histories of heavy cocaine use with the nine “experimenters.” The cocaine users showed a trend toward increased likelihood of a hospitalization for a psychiatric condition (67 versus 2 2 2 , not significant), and were more likely to be medicated for a medical problem (Fisher’s exact test = 5.8, df = 1, p < .02). These included endocarditis, a seizure disorder, and an ulcer. The eight patients who had been
COCAINE-ASSOCIATEDPANIC ATTACKS
59
Table 1. Comparison of Methadone Patients Having Panic Attacks Who Have Used Cocaine Heavily to Cocaine “Experimenters” with Panic Attacks
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
Cocaine use groups Characteristics
Heavy users
Experimenters
Total
Number Mean age (years) Percent male Psychiatric hospitalization ( 96) Medical illness (96) Depression (96) Duration of panic attacks (years) Agoraphobia (96) Alcohol use (%) Marijuana use (46)
9 39 33 67 89 89 10.7 56 56 67
9 35.7 56 22 33 89 10.4 66 63 89
18 37.3 f 5.8 44 44 6Ia 89 10.5 + 7.5 61 59 78
aFisher’s exact test = 5.8,df = I. p < .02.
HIV tested were seronegative. Five of our nine heavy cocaine users reported that cocaine use preceded the development of panic attacks. A large number, 15 of the 18 patients with panic disorder, reported a psychiatric disorder in a first degree relative. Eleven reported relatives who were psychiatrically hospitalized; 12 reported relatives who they thought suffered from panic attacks. While the literature suggests that family history reports tend to underestimate rates of most disorders [4], our patients’ estimates appeared to be exaggerated. Two of the relatives who reportedly suffered from panic attacks were interviewed by M.R., and, while anxious, they did not qualify as having panic attacks. Fourteen reported relatives who were clinically depressed, and four had relatives who made suicide attempts.
DISCUSSION Our 6- 13 % prevalence of panic disorder in methadone-maintained patients is at least fivefold greater than it was 10 years ago. Rounsaville et al. [3] screened 120 patients at the Yale Methadone Maintenance Program and found a lifetime 1 % incidence of panic disorder using the SADS-L and Research Diagnostic Criteria (RDC).Although the SCID with DSM-III-R was used in this study instead of the RDC (1977), there was only one patient who was included who would not have met the RDC criteria for panic disorder. His panic attacks coincided
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
60
ROSEN AND KOSTEN
with a major depressive episode, which excludes the diagnosis of panic disorder according to the RDC, but not in DSM-111-R. Our other patients easily met the RDC criteria for six attacks within 6 weeks, nervousness between attacks, and impairment as a result of panic attacks. The 1978 clinic sample had a median age of 32 years old, and 65% were male, which approximates current clinic demographics, although these study respondents included more females. Twenty percent of the patients reported using cocaine in the last 30 days; the rate of cocaine-positiveillicit urines per month was 1.5% for this group [5]. Sixty-three of the 120 patients (53%) met lifetime criteria for cocaine abuse. By comparison, 27 of the 280 patients at our clinic had cocainepositive illicit urines for the month of June 1990.This 9.6% rate is significantly Other nonsystematic data higher than the 1.5% in 1978 (x2 = 13.2,p C .0oOl>. from our methadone program suggests marked rises in the number of methadonemaintained patients using cocaine since 1978.A 2.5-year follow-up of 142 patients admitted to methadone maintenance in 1980 showed that 661142 used more cocaine after 2.5 years on methadone, only 361142 used less, and just 401142 did not use cocaine [6]. One likely explanation for the increased rate of panic disorder is the high frequency of cocaine use in our patients. Everyone had at least experimented with cocaine, and a large number of our panic sufferers reported anxiety resembling a panic attack after cocaine use. This association has been reported by Louie et al. [2],and our patients who used cocaine heavily show some similarities to their sample. These heavy users show similar temporal relationships between their cocaine use and the attacks, with attacks persisting for years after cocaine use ceased. Louie et al. noted that only one of his 10 subjects complained of increased anxiety with marijuana use, and the 78% of our patients who use marijuana report that it relieves their anxiety. This would also be consistent with several theories of drug-precipitated panic attacks. One is the kindling theory that cocaine provokes epileptiform activity within the limbic system [7].Behavioral sensitization has also been proposed as a model for cocaine induction of panic disorder [8].A mechanism for this could be cocaine-induced norepinepherinedepletion, followed by postsynaptic supersensitivity. Louie et al. [2]argue for pharmacologicalkindling, rather than behavioral sensitization, because these patients’ panic attacks do not generalize to other stimuli, or extinguish after several months, as one would expect with sensitization. These patients’ high comorbidity for depression, agoraphobia, and psychiatric hospitalization suggests a complicated picture. However, our sample is concordant with studies showing a higher incidence of major depression in patients suffering from panic disorder and a high familial concordance between panic disorder
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
COCAINE-ASSOCIATED PANIC ATTACKS
61
and depression [9, 101. The high familial incidence of panic disorder in our cocaine-using patients suggests that some of these patients were genetically predisposed to develop panic disorder, an assertion supported by the fact that four of our nine “heavy” cocaine users report panic attacks preceding their cocaine use. Our patients panic disorder appears to be multidetermined, with contributing factors being genetic vulnerability, comorbidity with depression, polysubstance abuse, and environmental stress. Our patients show a high (56%) comorbidity for agoraphobia, however, as opposed to the rate of 20% in Louie’s patients. Perhaps Louie’s patients, who had had symptoms for an average of 2 years, had not been symptomatic for long enough to develop agoraphobia, while our patients had panic attacks for an average of 10.5 years. A long latency may occur between onset of attacks and agoraphobia in these drug-precipitated cases. Breier et al. [l 11 found that spontaneous panic attacks had a much shorter latency until onset of agoraphobia than nonspontanmus panic attacks. They attribute this phenomenon to the protection from agoraphobia afforded by a cognitive explanation for the attack. Cocaine users may thus protect themselves from agoraphobia initially by attributing their panic attacks to cocaine, and later become agoraphobic as their panic attacks occur more spontaneously. Cocaine may have therefore brought on one disorder-panic-and delayed the onset of another-agoraphobia.
ACKNOWLEDGEMENTS Support was provided by the National Institute on Drug Abuse grants PSO-DA04060, R01-DA04505, R01-DA05626, and RSDA-KO2-DA00112 (TRK).
REFERENCES [I] Aronson, T. A,, and Craig, T. J., Cocaine precipitation of panic disorder, Am. J. Psychiarry 143:643-645 (1986). [2] Louie, A. K., Lannon, R. A., and Ketter, T. A., Treatment of cocaine-inducedpanic disorder, Am. J. Psychiarry 146:40-44 (1989). [3] Rounsaville, B. J., Weissman, M.M.,Kleber, H.,et al., Heterogeneity of psychiatric diagnosis in treated opiate addicts, Arch. Gen. Psychiarry 39:161-166 (1982). [4] Andreasen, N. C., Endimtt, J., Spitzer, R. L., et al., The family history method using diagnostic criteria, Arch. Gen. Psychiarry 34:1229-1235 (1977). [5] Kosten, T. R., Gawin, F. H.,Rounsaville, B. J., et al., Cocaine abuse among opioid addicts: Demographic and diagnostic factors in treatment, Am. J. Drug Alcohol Abuse 12: 1-16 (1986). [6] Kosten, T. R., Rounsaville, B. J., and Kleber, H.D., Antecedents and consequences of cocaine abuse among opioid addicts: A 2.5-year follow-up, J. New.Mew. Dis. 176:176-181(1988).
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
62
ROSEN AND KOSTEN
[7]Abraham, H. A., Do psychostimulantskindle panic disorder Oetter)?, Am. J. fsychiany 143:1627 (1986). [8]Aronson, T. A., and Craig, T. J.. Drs.Aronson and Craig reply (letter), Am. J. Psychiurry 143:1628 (1986). [9]Breir, A., Charney, D. S., and Heninger, G. R., The diagnostic validity of anxiety disorders and their relationship to depressive illness, Am. J. Psychiurry 142:787-797 (1985). [lo] Leckman, J. F.,Weissman, M. M., Merikangas, K. R., et al., Panic disorder increases risk of major depression, alcoholism, panic, and phobic disorders in affectively ill families, Arch. Gen. fsychiurry 40:1055-1060 (1983). [lI] Breier, A,, Charney, D. S.,and Heninger, G.R., Agoraphobia with panic attacks, Arch. Gen. Psychiurry 43:1029-1035 (1986).
AM. J. DRUG ALCOHOL ABUSE, 18(1), pp. 57-62 (1992)
Cocaine-Associated Panic Attacks in Methadone-Maintained Patients Marc I. Rosen,* MD Department of Psychiatry Yale University New Haven, Connecticut 0651 1
Thomas Kosten, MD Substance Abuse Treatment Unit Department of Psychiatry Yale University New Haven, Connecticut 06519
ABSTRACT The incidence of panic attacks methadone-maintained patients has increased over a 10-year period from 1 to 6-13%. Cocaine use appears to be associated with this increase, although other environmental and constitutional factors may be contributory. Patients with cocaineassociated panic differ from other panic patients in rates of psychiatric hospitalization and medical illness, but not in depression, other drug use, or agoraphobia.
INTRODUCTION Cocaine has been noted in several recent reports to precipitate panic disorder in patients who had not previously suffered from panic attacks [ 1, 21. We have noticed more panic patients in the Yale Methadone Maintenance Clinics during the last 10 years, and studied whether cocaine was responsible. We also examined
*To whom requests for reprints should be addressed at Substance Abuse Treatment Unit, 27 Sylvan Avenue, New Haven, Connecticut 0651 1. Telephone: (203) 785-2154.
57
ROSEN AND KOSTEN
58
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
whether other comorbidity was more common among those patients whose panic attacks were precipitated by cocaine than among other panic patients.
METHOD The 280 patients in the long-term Yale Methadone Maintenance Program (stays range from 2 to 15 years) were screened by using a brief questionnaire asking whether the patient had ever had an anxiety attack, had three attacks in a 3-week period, or been treated for anxiety. Sixty-six of the 141 respondents answered yes to two of the three questions. These patients were then interviewed in more detail by using the Structured Clinical Interview for DSM-III-R (SCID) by M.R. to see if they satisfied DSM-111-R criteria for panic attacks. The 18 clients who met DSM-111-R criteria for panic attacks were then asked about other substance use, whether other substance use preceeded the onset of frequent (more than Wmonth) panic attacks, hospitalization for psychiatric reasons, episodes of depression with neurovegetative symptoms, and whether others in their immediate families suffered from psychiatric disorders, including substance abuse, suicide, depression, and panic attacks. The patients’ twice monthly urine toxicology screens were reviewed to verify if recent sustance abuse had occurred. These results were compared with the incidences of panic disorder found in 1978 during a similar screening of 120 patients at the Yale Methadone Program [3].
RESULTS The most conservative prevalence of panic disorder is 6% (18/280), although among the 141 respondents the rate is 13% (n = 18) and the rate of self-reporting two out of three key panic symptoms is 46% (66/141). All of the 18 patients had used cocaine at some time in the past. Nine patients had at some time been “heavy” cocaine users (eight with several month periods of intravenous use; one who had free-based for several months). The other nine patients had used cocaine fewer than 10 times in their lives; these “experimenters” all denied cocaine use within the past year. Table 1 compares the nine patients with histories of heavy cocaine use with the nine “experimenters.” The cocaine users showed a trend toward increased likelihood of a hospitalization for a psychiatric condition (67 versus 2 2 2 , not significant), and were more likely to be medicated for a medical problem (Fisher’s exact test = 5.8, df = 1, p < .02). These included endocarditis, a seizure disorder, and an ulcer. The eight patients who had been
COCAINE-ASSOCIATEDPANIC ATTACKS
59
Table 1. Comparison of Methadone Patients Having Panic Attacks Who Have Used Cocaine Heavily to Cocaine “Experimenters” with Panic Attacks
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
Cocaine use groups Characteristics
Heavy users
Experimenters
Total
Number Mean age (years) Percent male Psychiatric hospitalization ( 96) Medical illness (96) Depression (96) Duration of panic attacks (years) Agoraphobia (96) Alcohol use (%) Marijuana use (46)
9 39 33 67 89 89 10.7 56 56 67
9 35.7 56 22 33 89 10.4 66 63 89
18 37.3 f 5.8 44 44 6Ia 89 10.5 + 7.5 61 59 78
aFisher’s exact test = 5.8,df = I. p < .02.
HIV tested were seronegative. Five of our nine heavy cocaine users reported that cocaine use preceded the development of panic attacks. A large number, 15 of the 18 patients with panic disorder, reported a psychiatric disorder in a first degree relative. Eleven reported relatives who were psychiatrically hospitalized; 12 reported relatives who they thought suffered from panic attacks. While the literature suggests that family history reports tend to underestimate rates of most disorders [4], our patients’ estimates appeared to be exaggerated. Two of the relatives who reportedly suffered from panic attacks were interviewed by M.R., and, while anxious, they did not qualify as having panic attacks. Fourteen reported relatives who were clinically depressed, and four had relatives who made suicide attempts.
DISCUSSION Our 6- 13 % prevalence of panic disorder in methadone-maintained patients is at least fivefold greater than it was 10 years ago. Rounsaville et al. [3] screened 120 patients at the Yale Methadone Maintenance Program and found a lifetime 1 % incidence of panic disorder using the SADS-L and Research Diagnostic Criteria (RDC).Although the SCID with DSM-III-R was used in this study instead of the RDC (1977), there was only one patient who was included who would not have met the RDC criteria for panic disorder. His panic attacks coincided
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
60
ROSEN AND KOSTEN
with a major depressive episode, which excludes the diagnosis of panic disorder according to the RDC, but not in DSM-111-R. Our other patients easily met the RDC criteria for six attacks within 6 weeks, nervousness between attacks, and impairment as a result of panic attacks. The 1978 clinic sample had a median age of 32 years old, and 65% were male, which approximates current clinic demographics, although these study respondents included more females. Twenty percent of the patients reported using cocaine in the last 30 days; the rate of cocaine-positiveillicit urines per month was 1.5% for this group [5]. Sixty-three of the 120 patients (53%) met lifetime criteria for cocaine abuse. By comparison, 27 of the 280 patients at our clinic had cocainepositive illicit urines for the month of June 1990.This 9.6% rate is significantly Other nonsystematic data higher than the 1.5% in 1978 (x2 = 13.2,p C .0oOl>. from our methadone program suggests marked rises in the number of methadonemaintained patients using cocaine since 1978.A 2.5-year follow-up of 142 patients admitted to methadone maintenance in 1980 showed that 661142 used more cocaine after 2.5 years on methadone, only 361142 used less, and just 401142 did not use cocaine [6]. One likely explanation for the increased rate of panic disorder is the high frequency of cocaine use in our patients. Everyone had at least experimented with cocaine, and a large number of our panic sufferers reported anxiety resembling a panic attack after cocaine use. This association has been reported by Louie et al. [2],and our patients who used cocaine heavily show some similarities to their sample. These heavy users show similar temporal relationships between their cocaine use and the attacks, with attacks persisting for years after cocaine use ceased. Louie et al. noted that only one of his 10 subjects complained of increased anxiety with marijuana use, and the 78% of our patients who use marijuana report that it relieves their anxiety. This would also be consistent with several theories of drug-precipitated panic attacks. One is the kindling theory that cocaine provokes epileptiform activity within the limbic system [7].Behavioral sensitization has also been proposed as a model for cocaine induction of panic disorder [8].A mechanism for this could be cocaine-induced norepinepherinedepletion, followed by postsynaptic supersensitivity. Louie et al. [2]argue for pharmacologicalkindling, rather than behavioral sensitization, because these patients’ panic attacks do not generalize to other stimuli, or extinguish after several months, as one would expect with sensitization. These patients’ high comorbidity for depression, agoraphobia, and psychiatric hospitalization suggests a complicated picture. However, our sample is concordant with studies showing a higher incidence of major depression in patients suffering from panic disorder and a high familial concordance between panic disorder
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
COCAINE-ASSOCIATED PANIC ATTACKS
61
and depression [9, 101. The high familial incidence of panic disorder in our cocaine-using patients suggests that some of these patients were genetically predisposed to develop panic disorder, an assertion supported by the fact that four of our nine “heavy” cocaine users report panic attacks preceding their cocaine use. Our patients panic disorder appears to be multidetermined, with contributing factors being genetic vulnerability, comorbidity with depression, polysubstance abuse, and environmental stress. Our patients show a high (56%) comorbidity for agoraphobia, however, as opposed to the rate of 20% in Louie’s patients. Perhaps Louie’s patients, who had had symptoms for an average of 2 years, had not been symptomatic for long enough to develop agoraphobia, while our patients had panic attacks for an average of 10.5 years. A long latency may occur between onset of attacks and agoraphobia in these drug-precipitated cases. Breier et al. [l 11 found that spontaneous panic attacks had a much shorter latency until onset of agoraphobia than nonspontanmus panic attacks. They attribute this phenomenon to the protection from agoraphobia afforded by a cognitive explanation for the attack. Cocaine users may thus protect themselves from agoraphobia initially by attributing their panic attacks to cocaine, and later become agoraphobic as their panic attacks occur more spontaneously. Cocaine may have therefore brought on one disorder-panic-and delayed the onset of another-agoraphobia.
ACKNOWLEDGEMENTS Support was provided by the National Institute on Drug Abuse grants PSO-DA04060, R01-DA04505, R01-DA05626, and RSDA-KO2-DA00112 (TRK).
REFERENCES [I] Aronson, T. A,, and Craig, T. J., Cocaine precipitation of panic disorder, Am. J. Psychiarry 143:643-645 (1986). [2] Louie, A. K., Lannon, R. A., and Ketter, T. A., Treatment of cocaine-inducedpanic disorder, Am. J. Psychiarry 146:40-44 (1989). [3] Rounsaville, B. J., Weissman, M.M.,Kleber, H.,et al., Heterogeneity of psychiatric diagnosis in treated opiate addicts, Arch. Gen. Psychiarry 39:161-166 (1982). [4] Andreasen, N. C., Endimtt, J., Spitzer, R. L., et al., The family history method using diagnostic criteria, Arch. Gen. Psychiarry 34:1229-1235 (1977). [5] Kosten, T. R., Gawin, F. H.,Rounsaville, B. J., et al., Cocaine abuse among opioid addicts: Demographic and diagnostic factors in treatment, Am. J. Drug Alcohol Abuse 12: 1-16 (1986). [6] Kosten, T. R., Rounsaville, B. J., and Kleber, H.D., Antecedents and consequences of cocaine abuse among opioid addicts: A 2.5-year follow-up, J. New.Mew. Dis. 176:176-181(1988).
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/27/14 For personal use only.
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[7]Abraham, H. A., Do psychostimulantskindle panic disorder Oetter)?, Am. J. fsychiany 143:1627 (1986). [8]Aronson, T. A., and Craig, T. J.. Drs.Aronson and Craig reply (letter), Am. J. Psychiurry 143:1628 (1986). [9]Breir, A., Charney, D. S., and Heninger, G. R., The diagnostic validity of anxiety disorders and their relationship to depressive illness, Am. J. Psychiurry 142:787-797 (1985). [lo] Leckman, J. F.,Weissman, M. M., Merikangas, K. R., et al., Panic disorder increases risk of major depression, alcoholism, panic, and phobic disorders in affectively ill families, Arch. Gen. fsychiurry 40:1055-1060 (1983). [lI] Breier, A,, Charney, D. S.,and Heninger, G.R., Agoraphobia with panic attacks, Arch. Gen. Psychiurry 43:1029-1035 (1986).
