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Treatment of comorbid disorder and : Evidence for a panic... Jeffrey P Kahn; John R Meyers Psychiatric Annals; Jan 2000; 30, 1; Research Library pg. 29

Treatment of Comorbid and Schizophrenia: Evidence for a Panic

Jeffrey P. Kahn, MD; and John R. Meyers, MD

hy is it important to consider com or­ comorbidity, illnesses once thought to be distinct bid panic disorder in schizophrenia? from one another, such as obsessive-compulsive W After all, schi,wphrenia wreaks such disorder and schizophrenia, are now known to devastation on patients' lives that panic disorder have important areas of overlap. Some clinicians would seem trivial in comparison. However, clin­ use the term "schizo-obsessive disorder" to s5 9 ical experience and a growing literature suggest describe this condition. - Similarly, social that comorbid panic disorder may be a major has been suggested as an etiologic factor for determinant of distress and dysfunction across schizophrenia. 1O This article considers the treat­ many psychiatric disorders, including schizo­ ment of comorbid panic disorder and schizophre­ I 3d phrenia. - The recognition of panic disorder in nia and, in light of these new perspectives, the patients with schizophrenia is crucial for design­ possibility of a distinct "panic psychosis.,dl.l2psychosis.,dl,l2 ing effective treatment. In addition, panic disor­ Although this article is based on a growing body der may play a significant pathogenetic role in of research, it includes a substantial amount of some schizophrenic illness. clinical impression. During the past 30 years, the diagnosis of psy­ chotic disorders has become increasingly precise. COMORBIDITY OF PANIC DISORDER AND Symptoms that were once lumped together under SCHIZOPHRENIA one diagnosis are now accurately distinguished Many studies have examined the prevalence of from one another, with disorders such as psychot­ panic disorder in patients with schizophrenia. ic , delusional , and paranoid Reported rates range from 16% to 63%.13-20 There being properly differentiated.4 are several explanations for this broad range. These more specific diagnoses came into common First, the prevalence of panic disorder may differ use as better understood their symp­ among subtypes of schizophrenia. For example, tom clusters, natural history, and treatment panic is less frequent in undifferentiated schizo­ response. For example, the discovery of lithium phrenia and more frequent in paranoid schizo­ made the distinction between psychotic mania and phrenia.2oa Second, because schizophrenic sub­ schizophrenia far more clinically pressing. types may not be distributed uniformly across As a result of recent interest in psychiatricpsychiatriC treatment sites, the panic rate found by a particu­ lar investigator may be skewed. Third, different treatment sites could also have different levels of

Dr. Kahil ,>I> ClillicalClil1ical Assistallt Prol""orProt""or of Psychialry. Cornell UlIh'ersilyUllh'ersily treatment response, study participation, and l'v1cdlcul College. New York, Nev,) York. Dr. Meyers is a Fellow in Forensic P.'vcitltltrv.P.'vchltltrv. Neil' York·PresbVIcriall Hospital. New York. New York. Address patient articulation of symptoms. Finally, the rei",,'trei'Ylllt r;qllcst, to Jeffrey P. Kahil. MD. Clinical Assistallt Professor of tools used by investigators to assess panic differ Psycitiatrll,Psychiatrll, C,)n/ellC,)",e/l UIIIL'ersitll Medical Collegc.Co/lege. 300 Celltral Park West. New 'tJrk. Nt lOUN in their effectiveness (eg, SCIO vs SCIO-UP and

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SADS vs SADS-LA). None of these instruments is noid about leaving the house, an a substitute for a skillful interview, especially in might render him or her nonpsychotic but still view of the confusing concurrence of panic symp­ reclusive. toms with psychotic exacerbation. Thus, the ade­ (luacy or inadequacy of the interview may also DIAGNOSIS OF PANIC DISORDER IN SCHIZOPHRENIA contribute to the difference in prevalence. To make the diagnosis of panic disorder, the Beyond studies of comorbidity, Heun and clinician must possess specific interviewing skills Maier's19 data suggest a familial aggregation of and be motivated to investigate potential panic panic disorder and schizophrenia, raising the symptoms. 1 Among actively psychotic patients, possibility of a panic-related etiology for at least the exploration may begin with questions about some cases of schiLophrenia. psychotic phenomena potentially related to panic symptoms. For example, consider the patient CLINICAL PERSPECTIVES ON NATURAL HISTORY who has intermittently active auditory hallucina­ Impressionistically, the rate of panic disorder tions. The patient is asked to focus on the nature among patients with schizophrenia in state hos­ of the voice(s). Do they begin, change, or become pital wards, emergency rooms, outpatient clinics, louder in a paroxysmal fashion? The patient is and the private office is closer to the higher end of then asked to focus on that paroxysmal moment. the epidemiologic estimates. Moreover, patients Does the patient also notice the sudden onset of often report retrospectively that panic , , , or was part of a prodromal phase before their psy­ ? The clinician should acknowledge that such chosis.21 For example, after a few months or years symptoms may well be related to the onset of of panic attacks, the episodes begin to take on voices. If such a pattern is present, the paroxys­ new symptoms of confusion, fearfulness, or para­ mal onset of voices should be considered a possi­ noia. Soon after, abrupt auditory ble marker for a , with voices as an are coincident with panic attacks. Not surprising­ added symptom. Other patients may experience ly, patients quickly become more attentive to the a paroxysmal increase in paranoid fear, which voices than to the other symptoms of panic disor­ may then be examined similady.Z2 For example, der. Commonly, the symptoms of panic disorder, one patient with schizophrenia, while in public, although continuing, are attributed to the voices would become abruptly more afraid that other or to another psychotic causality. Other psychotic people were reading her mind and plotting thoughts and paranoid may also be acutely against her. exacerbated during a panic attack. One patient During nonpsychotic periods, including peri­ believed she was actually being stabbed by some­ ods when antipsychotic is effective, one and that this was causing her chest pains. panic attacks may continue without psychotic fea­ Another described a "mind virus" that made her tures. The history of these episodes may be gath­ feel claustrophobic on buses. ered through more conventional (luestions about Patients with this kind of panic psychosis abrupt onset of panic, chest pain, tachycardia, or typically appear to have classic paranoid schizo­ shortness of breath. Commonly, nonpsychotic phrenia. Often, there is overlap with symptoms patients with schizophrenia also have symptoms related to comorbid diagnoses such as obses­ of panic disorder that are mistakenly labeled as sive-compulsive disorder. Psychotic symptoms medical diagnoses or mere physical complaints will usually respond in whole or in part when (eg, non cardiac chest pain, , asthma, and treated with antipsychotic medication alone. seizures). Because nonpsychotic panic attacks may Panic symptoms, however, will usually continue seem mild to the patient, careful inquiry is with absent or diminished psychotic features. required for diagnosis. Negative symptoms of social and emotional Finally, if a patient does have diagnoses of withdrawal typically persist. in at least some panic disorder and schizophrenia, it is useful to patients, the withdrawal may have an agorapho­ understand the chronology of symptoms. bic component. For example, if a patient is para- Patients often recall non psychotic panic attacks

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that preceded the onset of paroxysmal psychotic tient treatment, clonazepam might be started at a symptoms by months or years.} dose of 0.5 mg every 12 hours, and then gradual­ ly increased to achieve complete cessation of PHARMACOLOGIC TREATMENT panic-related symptoms. With close observation, Adjunctive has been used in the clinical benefit might be seen hours after the first 23 2 treatment of unselected schizophrenia. . .f In dose, although the full effect of a given dose of these studies, some patients experienced signifi­ clonazepam does not begin for at least 2 days. As cant reductions in positive and negative symp­ with panic disorder alone, the effective dose toms, whereas other patients were unaffected. ranges from 1 to 5 mg/ d, in divided and fixed These disparate responses were at first unex­ doses. Most patients will require between 2 and 4 plained. However, adjunctive alprazolam pro­ mg/ d. As-required dosing may be useful for duces a uniformly beneficial effect for patients determining the initial dose, but is less effective with both panic disorder and schizophrenia,ll,12 and more problematic beyond that point. suggesting that panic is not only a significant The addition of clonazepam has several bene­ marker for the response to alprazolam (and clon­ fits. Patients typically report a prompt reduction azepam) in schizophrenia, but also a pathogenet­ of anxiety. The cessation of panic attacks is typi­ ic contributor. cally associated with a further reduction in anx­ Effective pharmacotherapy begins with both iety, a reduction in phobia, increased social antipsychotic and antipanic . No spe­ interaction, and increased affective relatedness. cific antipsychotic appears to be more useful for These benefits are accompanied by, and may patients who have comorbid panic and schizo­ correspond to, a reduction in negative symp­ 3 phrenia. However, the newer atypical antipsy­ toms. ) At the same time, positive symptoms chotics are at least as effective as the older such as auditory hallucinations and paranoid , but have fewer side effects. may improve rapidly. In those Anecdotal evidence suggests that anti psychotics patients with a robust response to an anti panic worsen panic in some patients.25 Of the numerous medication, the requirements for antipsychotics antipanic medications currently available, clon­ may decrease as well. azepam and alprazolam are clearly superior. The patients who appear to have the best Clonazepam is preferred because of its longer response to the addition of antipanic pharma­ 26 27 half-life and lower potential for abuse. . Some cotherapy are those who have a shorter duration generic preparations of clonazepam may have of illness. In general, in all patients functional variable or reduced potency. improvement lags behind symptomatic improve­ Other antipanic medications include tricyclic ment. Similarly, fixed delusional beliefs are slow antidepressants (TCAs) and selective to respond, but, with ongoing treatment, may reuptake inhibitors (SSRIs), which may be effec­ gradually decline in significance for the patient. tive for the panic attacks of patients who have 28 3o both panic disorder and schizophrenia. . TREATMENT PRECAUTIONS However, TCAs and SSRls appear to be far less Although clonazepam has benefits, it also has effective for the concomitant reduction of positive drawbacks. Clonazepam may cause drowsiness and negative symptoms of schizophrenia. A con­ at the beginning of treatment, or with increases siderable body of research supports the adjunc­ in dosage. Although this sedation will diminish tive use of in the treatment of over time, patients often complain of tiredness. schizophrenia.23.31.32 However, only alprazolam This is an important concern for those patients and clonazepam appear to have substantial who drive or use machinery, or who take other anti panic effects, as well as substantial effects on sedating medications. Clonazepam may cause both positive and negative schizophrenic symp­ or contribute to gait disturbances and falls, espe­ toms. cially in patients with Clonazepam and anti psychotics may be start­ damage. Clonazepam, like all benzodiazepines, ed concurrently when indicated. During inpa- may cause and consequent

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risk of withdrawal symptoms. However, and long-term symptoms, the growth of new because it does not produce a "high," it has a opportunities, and the presence of emotional con­ lower potential for abuse, even among patients flicts that inevitably cloud these issues. Failure to who abu::.e or alcohol. Nevertheles::., cau­ provide proper support and will tion is warranted when prescribing clonazepam increase the likelihood of noncompliance and to patients who are substance abusers. The use treatment failure. 17 of clonazepam for the treatment of panic disor­ der does not lead to escalating dose require­ CONCLUSION AND FURTHER RESEARCH ments. Alprazolam has been reported to cause Panic disorder and schizuphrenia often occur manic excitation and dyscontrol in some comorbidly, and panic disorder has important patients, which is yet another reason for cau­ treatment implications. Adjunctive clonazepam 34 36 tion. · will often result in substantial improvement of Their response to medication may cause panic symptums and buth positive and negative patients with panic disorder and schizophrenia to symptoms of schizophrenia. A major impediment become noncompliant. The reduction of symp­ to ongoing benefit is the psychological response toms may be distressing, especially among to symptom reduction, which needs to be patients with long-standing panic disorder and addressed in psychotherapy. schizophrenia. Initially, patients are often delight­ The comorbidity of panic disorder, its pre­ ed that their symptoms are improving. However, morbid occurrence, the concurrence of panic after several weeks, their complaints of side attacks with psychotic exacerbation, and the effects and drowsiness increase, although the global response to anti panic treatment all sug­ sedative effect of clonazepam is likely to have gest that panic disorder may have a pathogenet­ diminished by then. The clinician should ic relationship to schizophrenia. For example, acknowledge the side effects, recognize the one patient with schizophrenia but without changes in the patient's life, and explore ways to apparent panic disorder underwent a 35% car­ help the patient adapt. Because outpatients are bon dioxide challenge to assess for panic (J. P. more difficult to monitor than inpatients and Kahn, MO, unpublished data, 1988).38 The receive less psychotherapeutic support, they patient responded with panic and auditory hal­ should be given lower doses of clonazepam ini­ lucinations. As a result of this experience, she tially and these doses should be increased more was able to describe similar panic symptoms gradually. concurrent with previous hallucinations, and As patients' conditions improve, other comor­ also preceding the initial onset of her psychosis. bid diagnoses must be reassessed, including Adjunctive alprazolam then produced marked obsessive-compulsive disorder, social phobia, clinical improvement. and . This is but one kind of research that could help us to understand the relationship between panic PSYCHOTHERAPY disorder and schizophrenia. Other avenues might The symptoms of panic disorder and schizo­ include the clinical analogy to amphetamine psy­ phrenia are usually overwhelming to patients chosis12 and the commonality of dopaminergic and have profound effects on their cognition, per­ and GABAergic mechanisms in both panic disor­ sonal relationships, and daily functioning. The der and schizophrenia.1 Well-designed studies are longer the symptoms last, the more familiar and needed to explore, confirm, and expand these extreme they become. Effective pharmacotherapy observations about panic disorder and schizo­ can be a double-edged sword. Although it may phrenia. In particular, phenomenology, natural relieve long-standing symptoms, often the history, diagnosis, treatment, and underlying patient's world becomes an unfamiliar place. Life pathophysiology need further examination. It becomes both more pleasant and more frighten­ may well be that some cases that are currently ing. To be effective, psychotherapy must address considered schizophrenia are actually panic psy­ the reduction and / or disappearance of severe chosis.

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