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Panic Disorder
American Description |
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Diagnostic Criteria
- Recurrent unexpected Panic Attacks
Criteria for Panic Attack:
A discrete period of intense fear or discomfort, in which four (or more) of
the following symptoms developed abruptly and reached a peak within 10
minutes:
- palpitations, pounding heart, or accelerated heart rate
- sweating
- trembling or shaking
- sensations of shortness of breath or smothering
- feeling of choking
- chest pain or discomfort
- nausea or abdominal distress
- feeling dizzy, unsteady, lightheaded, or faint
- derealization (feelings of unreality) or depersonalization (being
detached from oneself)
- fear of losing control or going crazy
- fear of dying
- paresthesias (numbness or tingling sensations)
- chills or hot flushes
- At least one of the attacks has been followed by 1 month (or more) of one
(or more) of the following:
- persistent concern about having additional attacks
- worry about the implications of the attack or its consequences (e.g.,
losing control, having a heart attack, "going crazy")
- a significant change in behavior related to the attacks
- The Panic Attacks are not due to the direct physiological effects of a
substance (e.g., a drug of abuse, a medication) or a general medical
condition (e.g., hyperthyroidism).
- The Panic Attacks are not better accounted for by another mental disorder,
such as Social Phobia (e.g., occurring on exposure to feared social
situations), Specific Phobia (e.g., on exposure to a specific phobic
situation), Obsessive-Compulsive Disorder (e.g., on exposure to dirt in
someone with an obsession about contamination), Posttraumatic Stress
Disorder (e.g., in response to stimuli associated with a severe stressor),
or Separation Anxiety Disorder (e.g., in response to being away from home or
close relatives).
Panic Disorder With Agoraphobia
- Meets the criteria for Panic Disorder
- The presence of Agoraphobia:
- Anxiety about being in places or situations from which escape might be
difficult (or embarrassing) or in which help may not be available in the
event of having an unexpected or situationally predisposed Panic Attack
or panic-like symptoms. Agoraphobic fears typically involve
characteristic clusters of situations that include being outside the
home alone; being in a crowd or standing in a line; being on a bridge;
and traveling in a bus, train, or automobile.
Note: Consider the diagnosis of Specific Phobia if the
avoidance is limited to one or only a few specific situations, or Social
Phobia if the avoidance is limited to social situations.
- The situations are avoided (e.g., travel is restricted) or else are
endured with marked distress or with anxiety about having a Panic Attack
or panic-like symptoms, or require the presence of a companion.
- The anxiety or phobic avoidance is not better accounted for by another
mental disorder, such as Social Phobia (e.g., avoidance limited to
social situations because of fear of embarrassment), Specific Phobia
(e.g., avoidance limited to a single situation like elevators),
Obsessive-Compulsive Disorder (e.g., avoidance of dirt in someone with
an obsession about contamination), Posttraumatic Stress Disorder (e.g.,
avoidance of stimuli associated with a severe stressor), or Separation
Anxiety Disorder (e.g., avoidance of leaving home or relatives).
Panic Disorder Without Agoraphobia
- Meets the criteria for Panic Disorder
- Absence of Agoraphobia
Associated Features
- Depressed Mood
- Somatic/Sexual Dysfunction
- Addiction
- Anxious/Fearful/Dependent Personality
Differential Diagnosis
Anxiety Disorder Due to a General Medical Condition; Substance-Induced Anxiety
Disorder; other Anxiety Disorder; Psychotic Disorders; Social Phobia; Specific
Phobia; Obsessive-Compulsive Disorder; Posttraumatic Stress Disorder; Separation
Anxiety Disorder; Delusional Disorder.
Internet Mental Health (www.mentalhealth.com)
copyright © 1995-1997 by Phillip W. Long, M.D.
The ICD-10 Classification of Mental and Behavioural Disorders
World Health Organization, Geneva, 1992
F41.0 Panic Disorder (Episodic Paroxysmal Anxiety)
The essential features are recurrent attacks of severe anxiety (panic) which
are not restricted to any particular situation or set of circumstances, and
which are therefore unpredictable. As in other anxiety disorders, the dominant
symptoms vary from person to person, but sudden onset of palpitations, chest
pain, choking sensations, dizziness, and feelings of unreality (depersonalization
or derealization) are common. There is also, almost invariably, a secondary fear
of dying, losing control, or going mad. Individual attacks usually last for
minutes only, though sometimes longer; their frequency and the course of the
disorder are both rather variable. An individual in a panic attack often
experiences a crescendo of fear and autonomic symptoms which results in an exit,
usually hurried, from wherever he or she may be. If this occurs in a specific
situation, such as on a bus or in a crowd, the patient may subsequently avoid
that situation. Similarly, frequent and unpredictable panic attacks produce fear
of being alone or going into public places. A panic attack is often followed by
a persistent fear of having another attack.
Diagnostic Guidelines
In this classification, a panic attack that occurs in an established phobic
situation is regarded as an expression of the severity of the phobia, which
should be given diagnostic precedence. Panic disorder should be the main
diagnosis only in the absence of any of the phobias in F40.
For a definite diagnosis, several severe attacks of autonomic anxiety should
have occurred within a period of about 1 month:
(a) in circumstances where there is no objective danger;
(b) without being confined to known or predictable situations; and
(c) with comparative freedom from anxiety symptoms between attacks (although
anticipatory anxiety is common).
Includes:
* panic attack
* panic state
Differential Diagnosis
Panic disorder must be distinguished from panic attacks occurring as part of
established phobic disorders as already noted. Panic attacks may be secondary to
depressive disorders, particularly in men, and if the criteria for a depressive
disorder are fulfilled at the same time, the panic disorder should not be given
as the main diagnosis.
ICD-10 copyright © 1992 by World Health Organization.
Internet Mental Health (www.mentalhealth.com)
copyright © 1995-1997 by Phillip W. Long, M.D.
From
Medscape Mental Health
Schizophrenia and Panic Disorder:
Epidemiology and Treatment
Samuel G. Siris, MD, Richard J. Pitch, MD, Paul C.
Bermanzohn, MD
Samuel G. Siris, MD, is professor of psychiatry; Richard J. Pitch,
MD, is assistant professor of clinical psychiatry; and Paul C.
Bermanzohn, MD, is assistant professor of psychiatry at the
Hillside Hospital Division of the Long Island Jewish Medical Center
and the Albert Einstein College of Medicine, New York, NY.
Abstract
Relatively recently, it has become apparent that a small but
meaningful proportion of schizophrenic patients experience
paniclike symptoms as a component of their condition. The full set
of implications of this observation, in terms of its potential role in
the classification, epidemiology, course, biology, outcomes,
treatment, and general understanding of schizophrenia, remains to be
determined. It may be useful, however, for both clinicians and
researchers to be aware of this phenomenon and to incorporate this
awareness into their treatment and investigatory considerations.
[Medscape Mental Health 4(6), 1999. (C) 1999 Medscape, Inc.]
Introduction
Anxiety is often apparent in patients with schizophrenia. It can be
generalized, associated with particular situations, or paroxysmal. In
the last case, when accompanied by certain autonomic
manifestations, schizophrenic patients may experience the
phenomenologic equivalent of a panic attack. Such paniclike
manifestations, however, have only recently begun to be appreciated
and examined in patients with schizophrenia.[1]
This article examines the evidence that panic symptoms may occur
during schizophrenia and explores the potential utility of standard
antipanic treatments in this circumstance. It takes note of factors that
may have interfered with the recognition of panic symptoms in this
patient group in the past. It also discusses a possible
conceptualization of panic as one among several associated
syndromes that occur in persons with schizophrenia, which may be
useful in understanding the heterogeneity of schizophrenia while
contributing to testable etiologic and therapeutic hypotheses.
The Diagnosis of Panic
As determined by the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition (DSM-IV) criteria,[2] the cardinal feature
of a panic attack is a sudden, discrete period of intense fear or
discomfort that is accompanied by certain specific cognitive and/or
somatic symptoms. The cognitive symptoms include derealization or
depersonalization, fear of losing control of impulses or "going
crazy," and intense fear of impending catastrophe or dying. These are
cognitive symptoms that clearly overlap with the cognitive symptoms
that are frequently attributed to psychosis. The somatic symptoms of
panic include palpitations or tachycardia, sweating, trembling,
shortness of breath, choking or smothering sensations, chest pain,
nausea, dizziness or lightheadedness, paresthesias, and chills or hot
flashes. As articulated in DSM-IV, at least 4 of a list of 13
accompanying symptoms must occur abruptly and reach peak
intensity within 10 minutes to make the diagnosis of a panic attack.
The DSM-IV does not consider a panic attack by itself to be a
codable disorder, since it may occur in the context of a variety of
conditions. In panic disorder, panic attacks have to be recurrent
(without specification of the quantity of attacks as had been
attempted in Diagnostic and Statistical Manual of Mental
Disorders, Third Edition [DSM-III]), and at least some of the panic
attacks must be unexpected. Moreover, these attacks must not be
restricted to particular situations that would then make them better
explained by another disorder (ie, public speaking in social phobia;
heights, enclosed spaces, or animals in specific phobias; absences in
separation anxiety; or other specific stimuli relevant to
obsessive-compulsive disorder or posttraumatic stress disorder).
Beyond this, the patient must have persistent concern regarding
additional attacks, worry about the implications or consequences of
the attacks, or have a significant behavioral change related to the
attacks. The remaining criteria serve to exclude panic attacks caused
by substances or medical conditions. The criteria for defining panic
are all clinically descriptive, and the diagnosis is phenomenologic.
The presence of schizophrenia does not specifically disqualify a
diagnosis of panic disorder in DSM-IV--a change from DSM-III,
which has now officially opened up the co-occurrence of these
syndromes to investigation.
Clinical Relevance
In his analysis of Epidemiologic Catchment Area (ECA) data, Boyd[3]
pointed out that panic attacks bring more people into treatment than
any other mental disorder and that people with panic disorder are
heavy users of mental health services. Panic disorder is associated
with suicide attempts, alcohol abuse, depression, social impairment,
financial dependence, and visits to the emergency department.[4]
Among patients with schizophrenia or schizo-affective disorder and
postpsychotic depression, a lifetime history of panic attacks or panic
disorder was found to be associated with a history of suicidal
ideation.[5] Schizophrenic patients are already at increased risk for
these problems.
Panic disorder itself is known to be a treatable condition using a
number of pharmacologic and nonpharmacologic strategies.[6] A
large literature substantiates this in patients with nonschizophrenic
panic disorder. Therefore, it would be useful to know how commonly
panic symptoms occur in schizophrenia and whether any currently
available antipanic treatments might be beneficial and safe for
patients with schizophrenia who have co-occurring panic symptoms.
The Epidemiology of Panic in Schizophrenia
Although the literature is limited, the few reports that address the
question suggest that panic attacks are not uncommon in patients
with schizophrenia.
The single largest study that generated informative data concerning
the issue of panic attacks in patients with schizophrenia was the ECA
project of the National Institute of Mental Health. This study
involved 18,572 individuals contained in five separate community
samples. Diagnoses in this project were established using the
National Institute of Mental Health Diagnostic Interview Schedule
(DIS), a structured interview designed to be conducted by lay
interviewers and coded to approximate DSM-III diagnoses. Boyd[3]
examined these data and found, depending on the community, that
28% to 63% of subjects with schizophrenia reported panic attacks.
These rates were for panic attacks, not panic disorder, and Boyd was
careful to label the diagnoses in this study as DIS rather than DSM-III
disorders to avoid possible diagnostic discrepancies.
Subsequently, Tien and Eaton[7] reexamined the same ECA database
and found that panic attacks were associated, at a trend level (P =
.062), with an increased probability (relative risk = 2.28) of
developing schizophrenia by the time of a planned reassessment
interview 1 year later.
A community-based Canadian study,[8] which similarly used the DIS
interview instrument, also revealed a disproportionate co-occurrence
of schizophrenia and panic disorder, including the observation that
the panic disorder preceded the onset of schizophrenia. Despite a
low prevalence of both panic disorder (n = 24) and schizophrenia
(n=14) in the absence of each other, in the sample of 2144
household residents 18 years or older, this study identified an
additional 6 individuals with comorbid diagnoses for both panic
disorder and schizophrenia, demonstrating both an increased
prevalence of panic disorder in schizophrenia and an increased rate
of schizophrenia among those with panic with a strong level of
statistical significance.[8,9]
Several more targeted studies have also revealed substantive rates of
phenotypic panic attacks in populations diagnosed as having
schizophrenia. In a study using International Classification of
Diseases, Ninth Revision criteria and the structured clinical
interview for Diagnostic and Statistical Manual of Mental
Disorders, Revised Third Edition (DSM-III-R), Argyle[10] found that
7 (35%) of 20 individuals with chronic schizophrenia, who were
receiving maintenance outpatient clinic treatment, had regularly
occurring panic attacks. Moreover, 4 (20% of the original sample) of
these 7 patients met full panic disorder criteria. Additionally, 3 of
the patients with panic attacks had agoraphobia, as did 1 patient
without panic attacks. Argyle also examined social avoidance
symptoms in his cohort and found, among the 13 cases with
significant social avoidance, that 4 (20% of the total sample) had
typical social phobia, with the classic fears of appearing anxious and
being humiliated.
Bermanzohn and associates[11] reported on the prevalence of
associated psychiatric syndromes among continuing day treatment
patients with chronic schizophrenia or schizo-affective disorder,
diagnosed by DSM-IV criteria as validated by structured clinical
interview for DSM-III-R interviews. Twelve (32.4%) of the 37
patients in their report had panic attacks, and 8 (21.6%) met full
criteria for panic disorder. Five of 8 who met panic disorder criteria
had agoraphobia as well. Interestingly, approximately 60% of these
patients (58.3% of those with panic attacks and 62.5% of those with
panic disorder) were also considered neuroleptic-refractory in terms
of their putatively schizophrenic symptoms, and the authors raised
the question of whether associated psychiatric syndromes in general
may be associated with neuroleptic nonresponse and/or chronicity
among patients currently treated for schizophrenia.
Zarate and associates[12] examined 60 subjects who met DSM-IV
criteria for schizophrenia or schizo-affective disorder and found that
8 (13%) met current criteria for panic disorder, 5 (8%) with
agoraphobia and 3 (5%) without. They also examined lifetime rates
of panic disorder in this sample and found that the proportion
increased to 11 (18%) with histories of panic, 7 (12%) with
agoraphobia and 4 (7%) without.
Finally, Cutler and Siris[13] described a narrowly defined group of 45
patients with Research Diagnostic Criteria (RDC) defined
schizophrenia or schizo-affective disorder, who also had an
operationally defined syndrome of postpsychotic depression. Most
were outpatients in clinic treatment. Eleven (24.4%) of these
patients had panic attacks by RDC criteria. Although panic has been
associated with depression in the general population,[3,14,15] panic
patients in the Cutler and Siris sample were not distinguishable on
the basis of their degree of depression on the Schedule for Affective
Disorders and Schizophrenia Scale[16] or Brief Psychiatric Rating
Scale.[17] Patients with panic attacks were also not distributed
differentially on the basis of other features, such as severity of
delusions, hallucinations, thought disorder, negative symptoms, and
alcohol or other drug abuse, in this report; although, considering the
statistical power of a sample of this size, there is a limit to the
confidence level that can be attached to these negative findings.
Looking for relationships from a different perspective, Heun and
Maier[18] studied the family comorbidity of schizophrenia and panic
disorder by examining the aggregation patterns of these disorders in
first-degree relatives of patients and in control subjects. They found
an increased frequency of panic disorder in relatives of
schizophrenic patients without panic disorder compared with
controls and that the frequencies of panic disorder were equivalent
among the relatives of patients with schizophrenia, panic disorder,
and the combination. The authors took this finding to suggest that
familial vulnerability factors underlying schizophrenia might lead to
the expression of panic. The reverse was not supported in this
sample, however. That is, the frequency of schizophrenia was not
enhanced in relatives of patients with panic disorder.
Patient Assessment and Differential Diagnosis
It is relevant to recognize that a number of factors may have made it
difficult for clinicians and investigators to recognize panic
syndromes in patients with schizophrenia. Diagnostic reductionism
is one such factor. Hierarchical concepts have been subtly and not so
subtly imbedded into our diagnostic system. Among the factors that
have contributed to this is the fact that our system is categorical
rather than dimensional and therefore carries a bias, reinforced by
medical tradition, that each patient should have one and only one
diagnosis.[19,20] For example, DSM-III formalized this hierarchical
concept by disallowing the diagnosis of many psychiatric disorders,
panic disorder among them, if they were "due to" another disorder
such as schizophrenia. Inasmuch as anxiety symptoms could often
easily be interpreted as being "due to" the schizophrenic condition or
its sequelae (for example, persecutory beliefs), anxiety disorders
were generally not codiagnosed under this system once a patient
received the diagnosis of schizophrenia.
Two other factors that could obscure panic symptoms in
schizophrenic patients are patients' withholding descriptions of
relevant experiences because of a sense of shame or fear of being
hospitalized.[11] Schizophrenic patients may experience panic
symptoms as foreign or "crazy" -- even by their standards -- and they
may be correct in recognizing that a communication of the sense of
urgency that they experience may contribute to the decision by
clinicians that they require the support or protection of a hospital
environment. A final obvious obstacle to the recognition of a panic
syndrome in schizophrenic patients is the potential that panic
symptoms may become intertwined with cognitive psychotic
symptoms at the time they are expressed. These symptoms could,
therefore, be viewed as simply the reasonable affective component
of psychosis in patients who may have reduced communication skills
or other peculiarities in the domain of interpersonal rapport.
The pathognomonic symptoms of panic attacks experienced by
patients with schizophrenia, as well as associated anticipatory anxiety
and avoidance behaviors, seem to be essentially identical to the
corresponding symptoms reported by patients without
schizophrenia.[21] However, as noted, patients with schizophrenia
frequently communicate in odd or ineffective ways, making it
difficult to recognize the panic syndrome. Additionally,
schizophrenic patients may be prone to present panic symptoms with
a psychotic overlay, explaining it with or incorporating it into
delusional material.[21,22] Indeed, it is possible that the occurrence of
panic attacks may be associated with a corresponding increase in
delusions and hallucinations.[13,21]
In difficult cases, it is likely that the characteristic somatic
symptoms associated with panic attacks may provide valuable clues.
Case A: Ms. A is a 35-year-old, unemployed, single woman living
with her parents. She has a 15-year history of chronic paranoid
schizophrenia, with persecutory and referential delusions and
auditory hallucinations that have been almost continuous throughout
her illness and were refractory to multiple neuroleptics.
For the past several years, she also has had panic attacks, sometimes
unexpected but usually confined to the evenings or waking her up
during the night. Typically, she describes episodic terror that her
parents are dead or will be harmed. This is accompanied by
palpitations, sweating, shortness of breath, feeling smothered,
choking sensations, and derealization. She worries that, if they are
dead, she will be all alone and unable to take care of herself. She also
is sure that she would be accused of murdering them, and, because of
her schizophrenia history, no one would believe her innocence. She
thinks she would be confined to either jail or a state hospital for the
rest of her life. Her panic symptoms progress in intensity, usually
until she checks her parents' room to see if they are breathing, at
which point she usually feels reassured. Because these attacks occur
almost every night, she delays going to sleep and has difficulty
falling asleep, fearing both the attack itself and the sensation of being
alone.
Other anxiety syndromes besides panic, of course, can also present
in schizophrenia. These must be distinguished, and Table 1 outlines a
general differential diagnosis of anxiety in schizophrenia. This
differential includes the anxiety (often of a free-floating nature that
the patient cannot explain) associated with the prodrome of a fresh
episode of psychosis,[23] social phobia, agoraphobia,
neuroleptic-induced akathisia, anxiety associated with various
medical treatments or conditions, and substance-related anxiety,
including caffeinism and nicotine withdrawal. Anxiety and agitation
can also arise as a component or consequence of increased
psychosis. Patients may become frightened and/or hypervigilant, for
example, as a natural response to delusions of persecution or thought
broadcasting. They may also become fearful of losing control in
response to dangerous command hallucinations or become
frightened in anticipation of hospital confinement.
Since schizophrenic patients typically have difficulty negotiating the
intricate and subtle rules of social interaction, they are likely to be
victims of social anxiety as well. Social anxiety usually centrally
involves the fear of being embarrassed in front of others. If it is
coupled with avoidance behavior, panic attacks (occasional), and the
self-recognition that the fear is excessive, criteria may also be met
for the diagnosis of social phobia. Both social phobia and
agoraphobia may be very difficult to recognize in schizophrenia,
because there is likely to be such a large phenomenologic overlap
with "negative symptoms" or possibly paranoia. Although social
isolation is often attributable to either social skill deficits or
stimulus overload in schizophrenia, social anxiety may also be a
significant contributor to this problem.[24] Establishing why a patient
with an anxiety disorder without schizophrenia avoids certain
situations is crucial for diagnostic purposes.[25] Patients with panic
disorder might say they fear primarily that people will notice when
they are having a panic attack, whereas people with social phobia fear
embarrassment from the social exposure. This distinction may prove
to be important for schizophrenic patients as well, although it may
sometimes place a premium on clinical interviewing skills and
techniques to be able to determine it with accuracy.
Case B: Ms. B is a 49-year-old divorced psychologist with
late-onset chronic paranoid schizophrenia, now with prominent
negative symptoms but originally with complex paranoid and bizarre
delusions. She had a history of panic disorder with agoraphobia that
preceded the onset of her schizophrenia by more than 10 years. The
panic disorder was complicated by alcohol abuse, now in remission
for 1 year. She presented to a partial hospital program with chief
complaints of anhedonia, lack of spontaneity, poverty of thought, and
inability to travel on public transportation, which limited her access
to desirable activities. On admission, she described limited symptom
attacks, consisting of episodic fear of "becoming sick again"
associated with palpitations, lightheadedness, and the urge to escape.
She would worry at those times about being hospitalized. These
episodes occurred primarily on exposure to public transportation but
were also occasionally unexpected. Mrs. B also displayed significant
parkinsonian symptoms, including bradyphrenia, bradykinesia,
masked facies, and flat affect, which was difficult to tease out from
her deficit schizophrenic symptoms. She had no active delusions,
hallucinations, or formal thought disorder. She was not dysphoric and
lacked vegetative signs of depression. She was taking molindone
hydrochloride, 50 mg orally HS, with no other medications.
In the partial hospital program, lorazepam, 1.5 mg/d, was added, and
she received supportive and cognitive therapies in groups and
individually. Her panic symptoms were completely eliminated within
2 weeks. By the third week, she was able to travel independently on
the bus. The molindone hydrochloride dose was then lowered to 25
mg HS, with some improvement in spontaneity and motivation. Her
range of affective display expanded, and movements also became
more supple.
Akathisia is an extrapyramidal syndrome produced by antipsychotic
drugs and possibly other medications that can present as a phenocopy
of anxiety.[26] It can occur in either a blatant or more subtle (and
therefore more difficult to recognize) form. With akathisia, patients
experience a generally dysphoric state, including a sense of muscular
tension or motor restlessness, which often makes them appear
overtly fidgety. Furthermore, the propensity for initiating behavior,
which is a hallmark of akathisia, can lead patients to crossover social
boundaries and thereby involve themselves in awkward situations that
could additionally cause them to feel anxious.[27] This
extrapyramidally based symptom is, itself, often difficult to
distinguish from psychic anxiety, psychotic agitation, or even
agitated depression.
Many medical conditions can produce anxiety syndromes (eg,
arrhythmias, hypoglycemia, hyperthyroidism), and a substantial
number of nonpsychiatric medications can also lead to anxiety as an
adverse effect. Schizophrenic patients, of course, may also become
medically ill, and clinical leads need to be followed so that these
medical conditions can be detected and treated. Finally, substances
of abuse, including caffeine and nicotine, frequently contribute to
anxiety-type symptoms either as a result of use or as a component of
withdrawal.[28] Indeed, schizophrenic patients have been found to be
at increased risk for substance abuse.[29,30]
Relationship Between Panic and Psychosis
Logically, there are a variety of relationships possible between panic
and psychosis in patients: a psychosis diathesis or psychotic
experiences could lead to panic, a panic diathesis or panic
experiences could lead to psychosis, manifestations of both
psychosis and panic could be the separate products of some common
cause, and both psychotic and panic symptoms could be expressions
of the same illness in certain individuals or even the same symptom
itself viewed through different lenses (see the discussion that
follows concerning paranoia). Indeed, it is possible that all these
conceptualizations might be correct in different patients. But
different conceptualizations will lead to different models of
symptom organization and illness, including the question of whether
a "schizopanic" disorder should be considered analogous to
schizo-affective disorder.
One model that has been proposed, which could link panic and
psychosis in at least some patients, is the stress-vulnerability
model.[31,32] Within that model, vulnerability to psychosis of a
schizophrenic type constitutes a continuum, ranging from a tiny
fraction of individuals with enormous vulnerabilities to the majority
of the population with a negligible vulnerability. In between, there is
a small but important percentage of individuals with an intermediate
vulnerability. According to this model, any of a variety of stressors
could push an individual past his or her threshold point for the
expression of psychotic symptoms, if the stressor was of sufficient
magnitude. The stress itself could be of any sort: biological,
psychological, or social. Theoretically, a panic attack in an individual
who happened to have panic susceptibility as a coexisting diathesis
could also act as an endogenous stressor.[33,34] Indeed, if this were so
for patients with schizophrenia, the panic and psychosis diatheses
could interact in a dynamic way, creating a vicious cycle of
symptoms.
For example, it is easy to imagine how psychotic misinterpretations
of panic symptoms--a component of which is terror of impending
catastrophe even in nonpsychotic individuals--could readily manifest
similarly to what we know as paranoia. Bermanzohn and colleagues
(unpublished observations) reassessed the ECA data with just this
potential relationship in mind and discovered that schizophrenic
persons with panic attacks were almost three times more likely to
also have paranoia compared with those schizophrenic persons who
did not have evidence of panic. Furthermore, among
nonschizophrenic individuals, they found that the chances of having
paranoia was about 10 times greater among individuals who had panic
attacks than among those who did not. Interestingly, paranoia has also
be found to be associated with panic in studies of personality traits in
nonschizophrenic populations.[35,36]
Case C: Mr. C is a 22-year-old, single, black man who had been
diagnosed as having schizophrenia 5 years previously. When he came
to a partial hospital program, his diagnosis was changed to psychotic
disorder not otherwise specified, because on careful reassessment
the only "A" criterion in his history was frequent delusions of
persecution and reference. He also met full criteria for panic
disorder, obsessive-compulsive disorder, and a severe schizotypal
personality. Mr. C had spontaneous panic attacks but was especially
vulnerable to them whenever he went out of the house, particularly in
crowded situations. He was exquisitely sensitive to other people
glancing at him and would believe that they considered him "weird" or
"feminine." He would become angry that they were judging him.
Often, he would then become fearful, with palpitations, sweating,
muscular tension, dry mouth, and lightheadedness, and unable to
concentrate at all, feeling like his thoughts were "blocked." He
labeled these episodes "phase outs," and it took several interviews
before the entire panic syndrome could be elicited. Mr. C stated that
he felt very uncomfortable around crowds of people because he
feared they would stare at him and make him "paranoid." He also
feared he would respond by acting on violent retaliatory thoughts. In
trying to differentiate the panic symptoms from the other difficulties
he seemed to have in reality testing, he said, "I just can't tell where
the paranoia ends and the anxiety begins. They feel the same, all
mixed together."
In this last context, it is notable that, before panic disorder was
described as a separate entity, patients with this disorder were
frequently diagnosed as having schizophrenia.[37]
In a more general sense, of course, schizophrenic patients may be at
increased risk for anxiety, because they so frequently misinterpret
situations as dangerous, and this propensity may be further
exacerbated by their lack of adequate coping skills. Reduced capacity
to "gate" or filter out environmental stimuli may also lead them to be
overwhelmed and consequently experience fear. For patients with
panic disorder and schizophrenia, such factors could contribute to a
cycle of increasingly heightened anxiety and autonomic discharge,
culminating in a full-blown panic attack. When such a pattern
becomes established, patients may become progressively
hypervigilant of warning signs and evolve global avoidance behaviors
for the purpose of self-protection. In the face of such a sequence of
events, cognitive retraining, protected in vivo exposure, and
medication might all help break this vicious cycle with the initiation
of more adaptive coping strategies and improved functioning.
Treatment
A number of treatments, both pharmacologic and nonpharmacologic,
have been described in panic disorder among patients without
schizophrenia. Imipramine hydrochloride and alprazolam have the
strongest evidence base in terms of controlled medication
trials.[38,39] Alternative heterocyclic antidepressants, selective
serotonin reuptake inhibitors, monoamine oxidase inhibitors,
clonazepam, and valproate sodium also have substantive support in
the literature.[6] Specific nonpharmacologic therapies, particularly
cognitive-behavioral therapy, have additionally received extensive
support.[40-45] To date, however, no randomized, double-blind,
placebo-controlled trials have been published regarding the treatment
of panic attacks or panic disorder in schizophrenic patients. Instead,
anecdotal reports form the basis for what currently exists in the
academic literature on this subject.
The largest open prospective psychopharmacologic case series is
that of Kahn et al,[22,46] involving adjunctive alprazolam treatment of
schizophrenic patients with panic. In this series, 7 inpatients meeting
DSM-III criteria for both schizophrenia and panic disorder (if the
DSM-III exclusionary criteria were ignored) were treated openly
with alprazolam in a titration schedule (up to 0.5 to 0.75 mg four
times daily) for 3 weeks, during which time their neuroleptic doses
were held constant. Patients then had the alprazolam tapered
throughout 2 weeks and did not take the drug for an additional 3
weeks. Panic attacks were reduced during the alprazolam treatment
phase in all 7 patients and increased again after its withdrawal.
Interestingly, both positive and negative symptoms of schizophrenia
also improved and worsened in conjunction with the amount of panic
symptoms.
This outcome was similar to that described in a single case report of
a patient with chronic paranoid schizophrenia who experienced what
the patient himself described as "paranoid attacks."[47] These attacks
consisted of the classic stigmata of panic symptoms, including
cognitive and autonomic symptoms associated with simultaneous
exacerbations of delusions and hallucinations. Various manipulations
of antipsychotic medications had not been helpful, but when the
patient's condition was maintained with a stable neuroleptic regimen
and alprazolam was added (0.5 mg 3 times daily), the patient
experienced a prompt cessation of these attacks for more than 3
weeks. When the attacks returned in an attenuated form, a further
increase of the alprazolam (to 5 mg daily) then resulted in a more
sustained improvement of the patient in terms of panic, psychosis,
and overall functioning. In another case series involving 4 patients
with schizophrenia and panic, Argyle[10] reported inconsistent
response of panic symptoms to increasing neuroleptic doses, but
panic symptoms were reduced following augmentation with diazepam
(2.5 mg 3 times daily or 5 mg twice daily) in 2 patients and with
alprazolam (0.5 mg 3 times daily) in a third.
In terms of the above case descriptions, a variety of studies have
assessed the effectiveness of alprazolam for "negative symptoms" in
schizophrenia, especially since fearful avoidance behaviors could
present with phenotypic similarity to negative symptoms. These
studies have resulted in mixed findings.[48-51] Unfortunately, for our
current purposes, these studies did not specifically address the issue
of panic attacks. Therefore, the issue of what role, if any, panic may
have played in the successfully treated cases remains unaddressed
and unresolved.
The use of benzodiazepines has also been examined on a more
general level in schizophrenia, in general with inconsistent results.
Again, unfortunately, none of the patients in these studies were
preselected or stratified for on the basis of anxiety symptoms or
syndromes. Had this been the case, it is possible that the results
would have been more consistent and/or more informative.[34]
Some relevant reports, though, have been published involving
individual cases treated with adjunctive antidepressant medications.
Yeragani and colleagues[52] treated 2 patients with residual
schizophrenia who also had comorbid panic attacks that consisted of
discrete periods of intense anxiety accompanied by various
autonomic symptoms. The addition of imipramine hydrochloride, 50
mg/d, led to "moderate to marked improvement" in their panic
attacks, without modification of psychotic symptoms. Siris et al[53]
described 2 additional cases in which imipramine was beneficial to
patients with schizophrenia and panic disorder as defined by
DSM-III-R criteria (ignoring exclusion rules). These patients were
notable in that they also had significant depressive symptoms and
met operationalized criteria for postpsychotic depression. One
patient had received placebo in a 9-week double-blind study, without
appreciable symptomatic change before receiving imipramine
hydrochloride, titrated up to 150 mg/d openly. At that point, she
achieved a full remission of her psychotic, depressive, and panic
symptoms for the first time in 10 years. Subsequently, after 6
months, use of the imipramine was again discontinued, under
double-blind conditions, and all 3 categories of symptoms recurred
within a month. When adjunctive imipramine was then again
reinstituted, symptoms in all 3 domains improved again within 2 to 4
weeks, as did overall social functioning. This "A-B-A-B" treatment
design strengthens the evidence that the changes observed were
linked to imipramine's effectiveness. The second case presented in
this report did not use the A-B-A-B pattern of drug treatment, but in
this case imipramine hydrochloride, 200 mg/d, was administered
under double-blind conditions and similarly resulted in improvement
in functioning and in the reduction of panic, depressive, and
psychotic symptoms. One issue that should be clearly noted in all
these case reports is that the psychotic symptoms that these patients
demonstrated were residual and not florid. Administration of
adjunctive antidepressants to patients with florid or acute psychotic
symptoms may be counterproductive in patients with
schizophrenia.[34,54,55]
Psychosocial treatment data concerning panic in schizophrenia are
even more limited. Nevertheless, the scant reports that do exist
suggest the possibility of benefit to a targeted intervention. Arlow
and colleagues[56] suggest that cognitive behavioral therapy in a group
setting, with some modifications, may be useful. This report was
based on an open 16-week clinical trial that involved 8 patients who
met DSM-III-R criteria for both schizophrenia and panic disorder.
After the treatment course, panic symptoms were reduced in
frequency and intensity. There is also a single case study that could
be construed as being supportive of this approach in which a patient
with chronic schizophrenia, who was noted to have agoraphobia (but
without panic attacks), responded favorably to the combination of
behavior therapy and diazepam.[57]
Conclusion
As our diagnostic concepts concerning panic syndromes have
become clarified and our nosology has become more finely tuned,
clear evidence has emerged that a meaningful subset of
schizophrenic patients experience panic symptoms as a component
of their condition. This recognition has spurred interest and may
eventually lead to an improved taxonomy and approach to treatment.
Despite some early encouraging preliminary work, however, more
systematic study is required to demonstrate both safety and efficacy
of pharmacologic and psychosocial treatment approaches among
schizophrenic patients with paniclike symptoms. It is also possible
that awareness of panic symptoms in certain schizophrenic patients
could provide clues to the biological underpinnings of a component
of their condition and/or advance our models for understanding part
of the heterogeneity of this complex disorder.
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