AVAILABLE EFFECTIVE TREATMENTS
FOR PANIC DISORDER AND AGORAPHOBIA
AND SATISFACTION WITH TREATMENT

B. Bandelow, P.D. Dr., Dipl.-Psych.,
Consultant Psychiatrist, K. Sievert, Dr.M. Röthemeyer, G. Hajak, P.D. Dr., Consultant Psychiatrist ,L. Adler, Dr., Consultant Psychiatrist, and E. Rüther, Prof. Dr., Göttingen, Germany.

 

Correspondence:

PD Dr. B. Bandelow, Dept. of Psychiatry, The University of Göttingen, Germany

Abstract

In order to compare the current state of treatment of panic disorder and agoraphobia (PDA) with the recommendations derived from controlled studies, 100 PDA patients and 103 physicians, psychologists and psychotherapists were interviewed by means of structured interviews about the psychological and psychopharmacological treatments used in panic disorder. Both investigations revealed that psychological and pharmacological treatment modalities with proven efficacy are being under-utilized (e.g. cognitive behavior therapy, exposure therapy, tricyclic antidepressants, benzodiazepines or selective serotonin reuptake inhibitors). On the other hand, methods whose efficacy has not been proven are being widely applied. The retrospective interviews with the patients revealed that they were most satisfied with treatments that have been proven effective in controlled studies. Reasons for the inadequate use of proven treatment modalities could be insufficient knowledge, ideological issues or the fact that 40 percent of the health professionals did not accept the term "panic disorder" as defined by DSM-III. Treatment of panic disorder might be improved if more heed were taken of the results of clinical studies.

Keywords: Panic Disorder; Agoraphobia; Drug treatment, Psychological treatment

 

Introduction

Patients with panic disorder with or without agoraphobia (PDA) as defined by DSM-III-R can be effectively treated with psychological and psychopharmacological treatment modalities. For an overview, all 77 PDA studies that could be traced by computer-aided literature search were evaluated (update of study [2]). In Table 1 and Table 2, the results of controlled studies are listed. A summary of these results is presented in Table 3. As placebo treatments are usually highly effective in panic disorder [1], only studies should be taken into account that used a drug placebo, a "psychological placebo" or a "waiting list" condition as a control group. Treatments that have proven effective in such comparisons include: benzodiazepines (e.g. alprazolam [1]), tricyclic antidepressants (e.g. imipramine [7] or clomipramine [12]), irreversible MAO-inhibitors (e.g. phenelzine [22]), and serotonin reuptake inhibitors (e.g. fluvoxamine [4] or paroxetine [19]). A consensus conference of the National Institute of Mental Health has recommended these drugs for treatment of PDA [17]. Neuroleptics are being widely applied in anxiety disorders in Europe, though their efficacy has not been shown in PDA trials. Treatment studies with beta blockers have shown conflicting results; in summary, convincing proof of efficacy is missing. Propranolol was not better than placebo and less effective than alprazolam [16]. In another study, it was less effective than diazepam [18]. Herbal preparations or homoeopathic formulations have not been investigated.

Psychological methods with proven efficacy include behavioral therapies like exposure or cognitive therapy [3; 6]. Other behavioral techniques like systematic desensitization [26] or progressive relaxation [11] were less effective than exposure therapy [13-15]. Psychodynamic psychotherapy was only investigated once in PDA patients: in that study, a combination of psychodynamic therapy and exposure was superior to pure psychodynamic therapy [10]. Other psychological therapies, e.g. client-centered therapy [20], autogenic training [21] or bio-feedback [9] have never been investigated in PDA patients.

Comparisons of psychological and psychopharmacological therapies have been discussed in detail by Bandelow et al. [2]. The number of such comparisons is low, and their results are conflicting. In summary, no major advantage of either method can be found. Because of the low numbers of follow-up investigations, the widely held opinion that psychological therapies are more effective at follow-up when compared to drug therapy cannot be proved. Though it is sometimes emphasized that simultaneous application of psychopharmacological drugs could inhibit psychological therapy, studies have shown that a combination of both modalities seems to be advantageous [25].

To compare the results of clinical research with the state of treatment in reality, two interview studies were conducted: first, among PDA patients, and second, among health professionals treating these patients. Patients were asked which therapeutic modalities had been applied to them and whether they felt these treatments had been effective. Physicians, psychologists and psychotherapists treating panic patients in their daily practice were asked about their treatment preferences.

 

Study 1: Patient Interviews

Methods

One hundred patients with current or remitted DSM-III-R panic disorder and or agoraphobia were asked to report on any drug and psychological treatment they received in the course of their illness. Ninety patients were former or present clients of the anxiety disorders unit of the University of Göttingen, Germany. These patients were contacted by mail or at a visit in the unit. Moreover, attempts were made to conatact all PDA patients presently being treated in the urban inpatient units treating anxiety patients. Thus, 10 additional patients who were being treated in psychiatric or psychosomatic hospitals at present could be questioned. Of 207 patients contacted, 24 were not traceable. Eighty-three gave their consent to the interview. Patients were questioned by means of a structured interview concerning the pharmacological and psychological treatment modalities they had received during the course of the illness. Self-applicable treatments such as autogenic training were also evaluated. Single acute treatments of panic attacks (e.g. emergency treatments with benzodiazepine injections) were not analyzed. Only treatments that were well remembered by the patients were evaluated. Treatments that were given either in a subclinical dose or not long enough to be effective were included. For tricyclic antidepressants (TCAs), selective serotonin inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs) only treatments with a minimum duration of four weeks continuous intake were evaluated. For benzodiazepines, neuroleptics and herbal preparations, a minimum intake duration of one week was required. Of 241 drug treatments reported by the patients, 28 were not evaluable because of this criterion. For all psychological treatments a minimum treatment duration of 8 weeks was necessary for inclusion. For inpatient treatment in a psychological treatment unit, a minimum duration of 4 weeks was required. Five psychological treatments out of 103 had to be excluded because of insufficient duration.

Patients were asked to indicate their satisfaction with a certain therapy by responding to the statement, "this therapy has been very helpful against my fear" on a 5-point Likert scale (from 0 = "not true" to 4 = "true"). As the scale was assumed to be of ordinal rank level, the central tendency ("mean") of these answers was taken as a "satisfaction index". Central tendencies were compared with Mann-Whitney’s U test. Statistical analysis were performed with the Statistical Analysis System (SAS 6.08, SAS Institute, Heidelberg).

Finally, 54 patients who had received both drugs (not including herbal preparations) and psychological treatments in the course of the illness had to indicate which kind of treatment had helped most in the course of the illness. Only one answer was possible to this question.

Results

Frequency of Application of Treatments

Four percent of the patients had not received any treatments before the interview. Eighty-eight percent of the patients had received drug treatments in the course of their anxiety disorder. All together 213 drug treatments were evaluated. A list of substance groups applied on the patients is shown in Table 4. Benzodiazepines were the most frequently used drugs, followed by tricyclic antidepressants and herbal preparations. Among the benzodiazepines, diazepam (21 %) and lorazepam (13 %) were used most frequently, among tricyclic antidepressants doxepine (18 %) and imipramine (10 %). The most used neuroleptic drug was fluspirilene (18 %).

The percentage of patients who received a certain psychological treatment is given in Table 5. Fifty-eight percent of the patients had received one of the indicated psychological treatments. A large number of patients (28 %) could not indicate the specification or „school" of psychological therapy applied to them. None of these patients reported the application of behavior techniques like exposure.

Drug prescription by general practitioners and other non-psychiatrists

Non-psychiatrists (general practitioners, internists and others) showed a different prescription profile, as reported by the patients. Benzodiazepines, neuroleptics, and herbal preparations were more often prescribed by non-psychiatrists as compared to psychiatrists, whereas psychiatrists tended to use more tricyclic antidepressants (Table 6).

Satisfaction with treatments

In Figure 1 the satisfaction with the different drugs applied as rated by the patients is shown. Benzodiazepines, SSRIs and tricyclic antidepressants were the most favored psychopharmacological drugs. The SSRIs were only used in 7 % so that the results may not be representative. Neuroleptics were not rated very highly, and herbal preparations and beta blockers were assessed as practically ineffective. In Table 7 the significant comparisons among drug therapies are given.

Among psychological therapies, behavior therapy was preferred (Figure 2). Satisfaction with this method was significantly higher than with psychodynamically oriented therapy (p < 0.005, U = 171, Bonferroni correction), "unknown therapy" (p< 0.005, U = 141) and autogenic training (p < 0.0001, U = 158).

Study II: Interviews with health professionals

Method

In this survey, practicing physicians, psychologists and psychotherapists who treat panic disorder patients in the town of Göttingen, Germany, were approached: General practitioners, internists and other non-psychiatric physicians, psychiatrists/neurologists, psychologists as well as psychotherapists who are neither physicians nor psychologists. Göttingen, a town with a population of 125.000, has a high concentration of physicians, psychologists and psychotherapists due to the presence of a large university. All major psychological treatment modalities (like psychoanalysis, client-centered psychotherapy or cognitive/behavior therapy are available and are being taught by university instructors.

The respondents were sent a questionnaire that presented a symptom description of panic disorder and agoraphobia taken from the DSM-III-R and the ICD-10. It was stated that the described disorder was called „panic disorder with/without agoraphobia" according to DSM-III-R/ICD-10. Respondents were asked if they had treated such patients in their office. Only one respondent answered that he had never treated panic patients and was excluded from the study. Furthermore, the respondents were requested to specify their qualification and duration of the education in medicine, psychology, psychiatry, or in psychological treatments. They were asked to indicate whether they accepted the term „panic disorder" as a diagnostic entity and as to their preferred pharmacological or psychological therapy.

Results

Of 104 questionnaires, 103 were evaluable. Of 103 respondents, 78 (76 %) were physicians, 22 (21 %) psychologists, one person was a physician and psychologist at the same time, and 2 were neither physicians nor psychologists but psychotherapists recognized by the insurance companies. Among the 78 physicians were 38 psychiatrists (specialists or trainees). Fifty-four percent of the physicians had a special education in psychological therapy which all physicians can acquire in Germany without necessarily being a psychiatrist. On average all respondents had seen 16.5 PDA patients in the past year (range 10-100; SD = 43,4). Psychiatrists named an average of 17.9 (range 5-100; SD 28.1) panic patients per year. Respondents stated an average of 11.3 years’ professional experience (range 0-39; SD = 8.4).

Most physicians indicated that they preferred tricyclic antidepressants in panic disorder treatment (Table 8). Second in line, herbal preparations are being prescribed. The prescribing patterns of psychiatrists and non-psychiatric physicians differ considerably: 74 % of the psychiatrists use tricyclic antidepressants, whereas only 24 % of the non-psychiatric physicians prefer these drugs. Herbal preparations and homoeopathic formulations are most popular among non-psychiatric physicians. Psychiatrists use more benzodiazepines than other physicians. Selective serotonin reuptake inhibitors, proposed by 24 % of the psychiatrists, are very rarely prescribed by non-psychiatric physicians (3 %). Psychologists are not allowed to write prescriptions.

The preference of the psychological therapists for the three major therapy schools is shown in Table 9 (as many psychotherapists are educated in more than one treatment modality and sometimes apply these methods simultaneously, the percentages do not add up to 100). Psychologists clearly prefer cognitive/behavior therapy over the two other therapy schools (no differentiation was made between cognitive therapy and traditional behavior therapy because a complex mixture of two is usually used in clinical practice). Among physicians, psychoanalysis was clearly preferred.

When asked as to their opinion about efficacy proofs, 43 % of the professionals who used psychodynamic therapy as a first line treatment for panic patients were convinced that their preferred method had been proven effective in controlled studies, whereas 89 % of the behaviorally oriented respondents thought that cognitive behavior therapy has been shown to be effective in such studies.

Acceptance of the term "Panic Disorder"

Of all respondents, 41 (40 %) stated that they would not agree in using the term „panic disorder" for the described syndrome (41 % of the psychiatrists, 23 % of the psychologists). The rejection of the term „panic disorder" was particularly high (73 %) in 22 respondents with psychoanalytic training, compared to 17 % of the 22 respondents with behaviorally oriented training.

Discussion

The treatment of patients with panic disorder and agoraphobia (PDA) could further be improved if the results of clinical studies were put into practice. This was shown in a survey among 100 patients with PDA and 103 health professionals treating PDA patients. Differences between the two surveys can be explained by the fact that the patients had to report retrospectively about their treatments, whereas the health professionals had to report about the state of their knowledge to date. Both results might be biased: the patients’ answers by the possibility that they did not remember the applied treatments very well, and the health professionals’ answers by the fact that they had the chance to inform themselves in the literature before filling out the questionnaire. Nevertheless, both surveys were consistent in showing that treatment modalities for which efficacy proofs exist were underutilized. On the other hand, treatment modalities that have never been investigated in PDA patients are being widely applied. For example, non-psychiatrists proposed herbal and homoeopathic preparations as a first-line treatment for panic disorder. A low incidence of adverse events is often offered as an argument for the use of these preparations. However, the choice of drug treatment should not be guided by side effects, but primarily by efficacy. If a prescriber puts his hope only in the placebo effect, an effective alternative treatment might be withheld from the patient.

In Germany it is common to treat anxiety disorders with neuroleptics, but proof of efficacy proofs is lacking for panic disorder patients. A consensus conference of the National Institute of Mental Health did not recommend neuroleptics for panic disorder. Nevertheless, one third of the patients reported having been treated with neuroleptics; even one third of the psychiatrists indicated that they use neuroleptics for treatment of panic disorder.

Though no convincing efficacy proofs exist for beta blockers, they were named by 26 % of the psychiatrists as a possible treatment option. On the other hand, only 6 % of the patients indicated that they had been treated with beta blockers.

Selective serotonin reuptake inhibitors were underrepresented in both surveys. The possible reason may be that SSRIs are relatively new on the market. Tricyclic antidepressants which are proposed as first line treatment in the literature have not even been tried in half of the patients. Only one quarter of non-psychiatrists, but three quarters of the psychiatrists reported prescribing these drugs.

Half of the patients (48 %) reported that they had received benzodiazepine treatment. Twice as many psychiatrists (45 %) as non-psychiatrists (22 %) reported prescribing these drugs. However, according to the statements of the patients, they had received even more benzodiazepine prescriptions from non-psychiatrists. In other countries benzodiazepines are more frequently prescribed to panic patients, as comparable studies in the United States [8] and in Canada [24] have shown.

Looking at proposed psychological therapies, under-utilization of effective methods is even more striking. Many patients were instructed to treat their disorder with autogenic training, though no proof of efficacy is available for this treatment modality. One third of the patients indicated they had been treated with depth psychology or psychoanalytic therapy. As stated above, the database for this treatment method is poor in spite of its wide-spread use.

A substantial number of patients could not indicate the psychological therapy school applied to them. In these cases patients were asked if specific techniques like exposure to fearful situations had been performed during sessions. In all cases, patients denied the use of such techniques so it can be excluded that these patients had been treated with behavior therapy.

Investigations in the USA and Canada also showed a lack of concordance between results of clinical studies and the current state of treatment [5; 8; 23; 24]. In Germany one reason for the uncritical use of ineffective treatment modalities may be insufficient knowledge, the other one may be that the new classification of anxiety disorders by DSM-III or ICD-10 does not find unequivocal acceptance: 40 % of the health professionals indicated that they would not accept the term „panic disorder" for the described symptom pattern. Acceptance of the modern DSM/ICD classification of the anxiety disorders by health care professionals treating these patients could help to improve the acceptance of research results.

The results of this retrospective investigation should be interpreted with caution because a number of factors could not be controlled in the study: proper recollection of applied therapies by the patients, adequate duration and dose of the drugs, compliance of drug intake, availability of psychological treatments, adequate duration of psychological treatments, classification level of therapists, assessment problems arising from combination treatments and many other factors. Most of the interviewed patients were clients of our psychopharmacological and behaviorally oriented anxiety disorders unit. This might have led to a distortion of the picture. Results might have been different if the interviews had mostly been conducted in an institution applying only psychological therapy. However, a comparable investigation was conducted in a mainly behavioral treatment institution and showed almost the same results [24]. Moreover, the statements of patients concerning the efficacy of treatments revealed that patients appreciated precisely those treatment methods that have been shown to be effective in controlled studies.

Another reason why the results should be interpreted with caution is the fact that patients do not have the same possibility to judge the risk/benefit ratio of certain treatments as health professionals do. Results may have been biased in favor of treatments showing immediate success, such as benzodiazepine treatment, as compared to treatments with delayed efficacy, like psychological therapies. Long-term effects such as possible addiction to benzodiazepines may not have been taken into consideration.

Much effort has been put into controlled studies on the efficacy of panic treatments. For the benefit of the patients concerned, the results of these investigations should be accepted by professionals treating panic disorder patients in order to improve the outcome of treatment.

 

Drug	Positive studies†	Negative studies*
Alprazolam	15	1
Imipramine	15	4
Fluvoxamine	6	0
Clomipramine	5	0
Paroxetine	3	0
Adinazolam, clonazepam, lorazepam, diazepam, sertraline	2	0
Amitriptyline, brofaromine, carbamazepine, citalopram, desipramine, etizolam, inositol, lofepramine, phenelzine, valproic acid, zimelidine	1	0
Propranolol	1	2
Bupropion, clonidine, ibuprofen, maprotiline, ritanserine, trazodone, verapamil	0	1
Buspirone	2	3

Table 1. Overview of the efficacy of drugs in panic disorder and agoraphobia (double-blind studies); †more effective than placebo or as effective as reference drug; *not more effective than placebo or less effective than reference drug

 

Psychological treatment	Positive studies†	Negative studies*
Cognitive therapy	6	2
Exposure therapy	3	2
Systematic desensitization	0	1

Table 2. Efficacy of psychological treatments in panic disorder and agoraphobia; †more effective than control condition; *no more effective than control condition

 

Drugs

Tricyclic antidepressants (e.g. imipramine, clomipramine)

Serotonin reuptake inhibitors (e.g. fluvoxamine, citalopram, paroxetine)

Benzodiazepines (e.g. alprazolam)

Irreversible MAO inhibitors (e.g. phenelzine)

Psychological therapies

Cognitive therapy

Exposure therapy (for agoraphobic patients)

Table 3. Overview: treatment modalities for PDA that have been shown to be effective in controlled trials

 

Drugs	Percent
Benzodiazepines	48%
Tricyclic antidepressants	42%
Herbal preparations	32%
Neuroleptics	29%
Serotonin reuptake inhibitors	7%
Beta blockers	6%
Tetracyclic antidepressants	3%
Irreversible MAO inhibitors	2%

Table 4. Percentage of PDA patients who received drugs in the course of their illness (n=100)

 

Psychological treatment	Percent
Autogenic training	43%
Psychodynamic therapy	33%
Unknown	28%
Cognitive/behavior therapy	20%
Biofeedback	6%
Progressive relaxation	6%
Hypnosis	4%

Table 5. Psychological therapies: frequency of application in percent

 

	n prescriptions	Psychiatrists	Non-psychiatrists	no prescription	unknown
Benzodiazepines	77	40.2 %	57.1 %	-	2.6 %
Tricyclic antidepressants	51	64.7 %	31.4 %	-	3.9%
Neuroleptics	30	33.3 %	63.3 %	-	3.3 %
Herbal preparations	37	10.8 %	54.9 %	35.1 %	0.0 %
Total	195	40.0 %	50.7 %	6.7 %	2.6 %

Table 6. Prescription of drugs by psychiatrists and non-psychiatrists (general practitioners, internists, and others)

 

	SSRI	TCA	Neuroleptics	Herbal preparations
Benzodiazepines	N.S.	N.S.	P < 0.001 (U=167)	P < 0.0001 (U=214)
SSRI		N.S.	N.S.	P < 0.005 (U=35)
Tricyclic antidepressants			P < 0.005 (U=381)	P < 0.0001 (U=248)
Neuroleptics				N.S.

Table 7. Significance of comparisons between different medications (Mann-Whitney’s U test; Bonferroni correction)

 

	All physicians (n=79)	Non-psychiatric physicians (n=41)	Psychiatrists (n=38)
Tricyclic antidepressants	48%	24%	74%
Herbal preparations	40%	46%	29%
Benzodiazepines	33%	22%	45%
Neuroleptics	24%	20%	29%
Beta blockers	20%	15%	26%
Homoeopathic formulations	18%	32%	3%
Serotonin reuptake inhibitors	13%	3%	24%
Irreversible monoamine oxidase inhibitors	8%	0%	16%
Others	1%	3%	3%

Table 8. Percentage of different groups of physicians who propose different drug groups (more than one choice possible)

 

Psychological therapy	All psychological therapists (n= 68)	All physicians (n= 49)	Psychiatrists (n= 33)	Psychologists (n= 22)
Psychoanalysis	44%	57%	51%	9%
Client-centered therapy (Rogerian)	28%	35%	33%	9%
Cognitive/behavior therapy	28%	4%	6%	64%

Table 9. Respondents practicing psychological therapies: treatment modality proposed in the first line

 

Figure 1. Mean satisfaction with drug therapy, indicated on a 5-point scale (from 0 = ‘not at all helpful’ to 4 = ‘very helpful’)

 

 

Figure 2. Mean satisfaction with psychological therapies, indicated on a 5-point scale (from 0 = ‘not at all helpful’ to 4 = ‘very helpful’)

 

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