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Antidepressants in panic disorder.

Panic disorder is a serious and common illness affecting 1% of the population at any one time. Comorbidity with depression may be as high as 40%. The illness has been recognized as a separate entity since the 1960s and treatment with tricyclics being used since that time. Tricyclics, monoamine oxidase inhibitors, benzodiazepines, beta-blockers and anticonvulsants have all been used with varying degrees of success. Until recently, tricyclics and benzodiazepines were the treatments of choice but selective serotonin reuptake inhibitors (SSRIs) have recently been studied intensively and, based on studies of citalopram and paroxetine, must now be considered first line therapy. Both SSRIs and tricyclics suffer from a long latency period, possibly as long as 12 weeks before maximal benefit is obtained, which is in contrast to the benzodiazepines that produce almost instant symptom relief. The dependency potential of the benzodiazepines, however, limits their usefulness. Paroxetine and citalopram have good efficacy data over both the short and long term and are effective at standard dosages, the most effective for citalopram being 20-30 mg. Both drugs performed better than the comparator tricyclic antidepressant (chlomipramine) and must now be considered current drugs of choice. Despite the superior efficacy of these drugs, however, many patients are poorly controlled and investigation of combination therapies for resistant panic disorder is needed.

Antidepressive Agents↗

Dental management of the adolescent with panic disorder.

Panic disorder is a psychiatric disease without obvious cause. It is accompanied by signs of terror, such as chest pain, palpitation, and shortness of breath. One of every 75 Americans is afflicted. Onset occurs most commonly during adolescence. Some infants and children exhibit anxiety-like responses, such as retreat and avoidance, and behavioral restraint when faced with unfamiliar people, objects, and events. Panel disorder has a special relevance for dentistry, because it is frequently associated with mitral valve prolapse. Furthermore, medications used to treat the disorder are associated with detrimental changes in the oral cavity and adverse interactions with dental therapeutic agents. The authors discuss the podromal characteristics of children at risk for panic disorder and the characteristics of the malady recognized by the American Psychiatric Association. Associated medical problems are also presented and discussed. A survey of ninth graders found as many as 12 percent had spontaneous panic attacks. Approximately 20 percent of all adults with the disorder report its onset before age ten. Etiology, medical and dental management are discussed.

Adolescent↗

Discontinuation reactions to alprazolam in panic disorder.

Panic disorder is a chronic illness with only some degree of spontaneous recovery. It is not surprising therefore that discontinuation of an effective medical treatment may be followed by relapse. Therefore the timing and methodology of discontinuing that treatment are now recognized as essential facets of optimal clinical management. In addition to relapse, rebound and the withdrawal syndrome have been reported with many psychotropic agents, particularly with the benzodiazepines. This paper discusses data from three discontinuation studies with alprazolam i.e. the Phase I Cross-National Collaborative Panic discontinuation study after short-term treatment, the Phase I discontinuation study after long-term treatment, and data from the Montreal site of the Alprazolam SR discontinuation study. Phase I of the Cross-National Collaborative Study of Panic Disorder investigated the discontinuation of alprazolam in two populations. There was an intensive, placebo-controlled, time-limited study of discontinuation after short-term treatment (8 weeks) in the first population. For the second, there was a less rigorous open follow-up of patients who had been treated for 5-12 months with alprazolam. The dose-reduction regimen of alprazolam in both studies was approximately the same--a 1 mg decrease every 3-7 days. In the short-term treatment study, 109 patients were treated for 8 weeks, tapered for 4 weeks and observed for another 2 weeks post discontinuation. Significant relapse in the alprazolam-treated group occurred during discontinuation. Rebound of panic attacks occurred in 27% of patients given alprazolam, and distinct transient withdrawal syndrome occurred in 35%. Indicative of the withdrawal syndrome were confusion, clouded sensorium, heightened sensory perception, dysosmia, paresthesias, muscle cramps, muscle twitch, blurred vision, diarrhea, decreased appetite, and weight loss. The clinical course in the alprazolam-treated patients revealed a marked exacerbation of symptoms during the end of the tapering period and the first week without medication, which was followed by improvement during the second post-taper week. In the long-term treatment study, 142 patients were treated with alprazolam for periods ranging from 5 months to 1 year (mean, 27.5 weeks). In this naturalistic study, 76% of the patients reported improvement, 6.3% reported no change, and 10.6% reported that they were worse. During discontinuation, 12.8% of the 128 patients whose dosage was tapered reported some kind of nonspecified withdrawal symptoms. Of the 142 patients, 47.2% were able to taper their medication dosage and to discontinue treatment; 19.7% tapered but restarted alprazolam shortly after discontinuation; 33.1% were unable or unwilling to taper or discontinue alprazolam.(ABSTRACT TRUNCATED AT 400 WORDS)

Agoraphobia↗

Role of elastin polymorphisms in panic disorder.

Panic disorder (PD) is a complex neuropsychiatric disorder that has been associated with an increased frequency of mitral valve prolapse. Elastin is a prominent component of mitral valves and, in a genome screen of 23 pedigrees with PD, we found evidence of linkage to the region of chromosome 7 that contains the elastin gene (ELN). Therefore, we examined the minimal essential promoter and coding regions of ELN in 23 independent probands from the families in our linkage studies using single strand conformational polymorphism analysis. We found three polymorphisms including one that coded for a non-conservative amino acid change. However, none of these polymorphisms were associated with panic disorder in a case-control analysis or linked to it in multiplex pedigrees. In our pedigrees, exonic polymorphisms in ELN do not play a major role in the genetic vulnerability to PD.

Base Sequence↗

Clomipramine and fluoxetine effects in the treatment of panic disorder.

Panic disorder (PD) is an acute psychobiologic reaction manifested by intense anxiety and panic attacks, that occur unpredictably with subjective sense of intense apprehension or terror, accompanied by temporary loss of the ability to plan, think, or reason and the intense desire to escape or flee the situation. Panic attacks may last from a few seconds to an hour or longer. Symptoms typically include, among others, palpitations, tachycardia, hypertension, chest pain, dyspnoea, and fear of loosing control or going crazy and vague feeling of imminent doom or death. Since pharmacotherapy of PD includes the administration of selective serotonin reuptake inhibitors and tricyclic antidepressants, the objective of this study was to perform a pilot double blind clinical trial designed to compare the effects of two studied drugs in the treatment of PD. A total number of 40 patients with a history of panic disorder were randomly assigned into two groups of 20 patients each. Hamilton anxiety rating scale and Standard Psychiatric Interview were methods for PD assessment. One group was treated with clomipramine hydrochloride (ANAFRANIL) 75 mg/day and the other with fluoxetine (OXETIN) 60 mg/day. Both drugs were administrated by mouth (PO) two times-a-day in equally divided doses for 6 weeks. Both studied agents produced similar antipanic effectiveness. Favourable response was achieved in 95% of patients treated with fluoxetine and 90% of patients treated with clomipramine. The onset of antipanic effects was quicker in all clomipramine treated patients, while fluoxetine produced more-favourable response in male patients. The duration of treatment with both antidepressants studied should be at least 10 weeks, instead of 6 weeks.

Journal Article↗

Association of panic disorder and panic attacks with hypertension.

PURPOSE: Previous studies of the association between hypertension and panic disorder were uncontrolled or involved small numbers of patients. PATIENTS AND METHODS: We compared the prevalence of panic disorder and panic attacks in 351 patients with documented hypertension who were randomly selected from all hypertensive patients registered in one primary care practice with age- and gender-matched normotensive patients from the same practice and with hypertensive patients attending a hospital clinic. All three groups completed questionnaires for panic disorder based on standard criteria, as well as the Hospital Anxiety and Depression scale. RESULTS: The prevalence of current (previous 6 months) panic attacks was significantly greater in primary care patients with hypertension (17%, P <0.05) and hospital-based hypertensive patients (19%, P <0.01) than in normotensive patients (11%). Similar results were seen for lifetime panic attacks (35% versus 39% versus 22%; both P for comparisons with normotensive patients <0.001). The prevalence of panic disorder was significantly greater in primary care patients with hypertension (13%) than normotensive patients (8%, P <0.05). Anxiety scores were significantly higher in both hypertensive groups than in normotensive patients. Depression scores were significantly higher in hospital-based hypertensive patients than in the other two groups. The reported diagnosis of hypertension antedated the onset of panic attacks in a large majority of patients (P <0.01). CONCLUSIONS: Physicians caring for patients with hypertension should be aware of the significantly greater prevalence of panic attacks in these patients.

Aged↗

Alcohol and anxiety: subtle and obvious attributes of abuse in adults with social anxiety disorder and panic disorder.

Previous research has found a relation between social anxiety disorder and alcoholism but recent work found no differences in drinking levels among socially anxious individuals, dysthymics, and normal controls. Using a more sophisticated measure of substance abuse may further explicate the relation between social anxiety and drinking. We examined aspects of substance abuse in treatment-seeking individuals with social anxiety disorder or panic disorder (psychiatric control group) as well as nondisordered individuals (normal control group). We used the Substance Abuse Subtle Screening Inventory-3 because it includes both face valid and subtle items to control for social desirability. Contrary to the hypotheses, there were few obvious or subtle aspects of substance abuse significantly greater for individuals with social anxiety disorder than those with panic disorder or normal controls. Implications for understanding the social anxiety-alcohol relationship, assessment of substance abuse in socially anxious populations, and the construct of social anxiety-are discussed.

Adult↗

Comorbid bipolar disorder and panic disorder in families with a high prevalence of bipolar disorder.

OBJECTIVE: Panic attacks are a common complication of affective disorder, although the etiologic relationship of panic and affective symptoms has not been determined. Evidence from a family study suggests that panic attacks and panic disorder may be related genetically to bipolar disorder. This study used diagnostic data from the NIMH Bipolar Disorder Genetics Initiative to assess in a separate, larger family set the familiality of panic combined with bipolar disorder. METHOD: First-degree relatives (N=966) of probands with bipolar I disorder (N=192) and schizoaffective disorder, bipolar type, (N=11) were included in the study. All subjects were interviewed directly and were assigned best-estimate diagnoses for major affective and other psychiatric disorders. The risk of a family member being diagnosed with panic disorder if the proband with bipolar disorder had panic attacks or panic disorder was calculated with logistic regression analysis with generalized estimating equations that controlled for sex and affective disorder subdiagnosis. RESULTS: More than 90% of the probands and first-degree relatives with panic disorder also had an affective disorder diagnosis. Panic disorder was present in 17% of the relatives with recurrent major affective disorder and in 3% of the relatives without recurrent major affective disorder. Risk of panic disorder in relatives with bipolar disorder was increased significantly if the proband had panic attacks or panic disorder. CONCLUSIONS: Risk for panic disorder with familial bipolar disorder appears to be inherited. Inherited risk for panic disorder with bipolar disorder may indicate a shared genetic etiology for both disorders in some families. The patterns of bipolar disorder and panic disorder comorbidity observed in families imply a complex genetic etiology, which may be elucidated by using endophenotypes.

Adult↗

Remission and relapse in subjects with panic disorder and panic with agoraphobia: a prospective short-interval naturalistic follow-up.

This article reports on the course of uncomplicated panic disorder and panic with agoraphobia on 309 patients participating in the Harvard/Brown Anxiety Research Project, a prospective longitudinal study of patients with DSM-III-R-defined anxiety disorders. At 1 year, there was a .39 probability of full remission for uncomplicated panic disorder and a .17 probability of full remission for panic disorder with agoraphobia Similar differences in time to remission for these syndromes were still found when criteria for remission were made less stringent. However, even requiring less improvement for remission left a large percentage of subjects in an episode, and for those that remitted, relapse occurred quickly, indicating a chronic and recurrent course of illness. This is the first longitudinal, prospective, naturalistic study on a large cohort of subjects with anxiety disorders to have regular, structured, short-interval follow-up. Our results are consistent with the view that panic disorder has a chronic course with high rates of relapse after remission and longer episodes when agoraphobia is a part of the constellation of symptoms.

Adult↗

Cognitive processing of idiographic emotional information in panic disorder.

Panic disorder patients, obsessive-compulsive disorder (OCD) patients, and normal control subjects performed a computerized Stroop color-naming task in which they named the colors of panic-threat words (e.g. Collapse), general-threat words (e.g. Infectious), positive words related to panic (e.g. Relaxed), and neutral words (e.g. Sleepy). Idiographic stimulus selection ensured their personal emotional relevance for each subject. In accordance with prediction, panic patients, but not OCD patients, exhibited greater interference for panic-threat words than for positive words related to panic and for neutral words. Panic patients did not respond differentially to panic-threat and general-threat words. Complexities concerning attentional bias research in the anxiety disorders are discussed.

Cognition↗

Prevalence, patterns and role of personality disorders in panic disorder patients with and without comorbid (lifetime) major depression.

A total of 84 consecutive out-patients from the Anxiety Disorders Clinic of the Psychiatric University Hospital in Graz with a current panic disorder were diagnosed for Axis I and II disorders using the Structured Clinical Interviews for DSM-III-R. The subjects were divided into two groups: (i) 49 patients who met the criteria for panic disorder with or without agoraphobia and had no history of an affective disorder and (ii) 35 patients who had a (lifetime) comorbidity of a major depressive disorder. There was a statistically significant difference in the prevalence of personality disorders between the two groups, which was due to the higher frequency of narcissistic personality disorder in the comorbid sample. Logistic regression analysis revealed that agoraphobia and/or major depression were associated with personality disorders, thus indicating that the relationship between panic disorder, agoraphobia and major depression is not straightforward, but is strongly influenced by the presence of Axis II disorders. Furthermore, the results of this study provide support for the 'unitary position' concerning the relationship between panic disorder and depression.

Adult↗

Evidence that variation in the peripheral benzodiazepine receptor (PBR) gene influences susceptibility to panic disorder.

Panic disorder (PD) is the repeated sudden occurrence of panic attacks, episodes characterized by psychological symptoms. Peripheral benzodiazepine receptor (PBR) is closely associated with personality traits for anxiety tolerance, and that it holds promise as a biological marker of stressful conditions. We have performed association analyses using the polymorphism to determine the PBR in PD. We screened the subjects for sequence variations within the 5' region, the coding region (exons 2-4), and the 3' noncoding region. One novel missense variant in exon 4, derived from the nucleotide transition in codon 162 (CGT --> CAT:485G > A) resulting in an arginine-to-histidine (Arg --> His) change, was detected in these subjects. The 485G > polymorphism of the PBR gene was analyzed in 91 PD patients and 178 controls. The genotypic and allelic analyses of the 485G > A revealed significant differences between the panic patients and the comparison subjects (P = 0.021 and 0.014, respectively). The present study provides new and important evidence that variation in the PBR gene influences susceptibility to PD.

Adult↗

Sleep in panic disorders.

Panic disorder is a common anxiety disorder, which has relatively often its onset during adolescence. Besides panic attacks and avoidance behavior the patients often have sleep disturbances. They suffer from insomnia, nocturnal panic attacks, fear of going to bed or falling asleep and drug- or alcohol-related symptoms such as withdrawal phenomena.

Adult↗

Cost-effectiveness of psychological and pharmacological interventions for generalized anxiety disorder and panic disorder.

OBJECTIVE: To assess from a health sector perspective the incremental cost-effectiveness of interventions for generalized anxiety disorder (cognitive behavioural therapy [CBT] and serotonin and noradrenaline reuptake inhibitors [SNRIs]) and panic disorder (CBT, selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]). METHOD: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analyses of randomised controlled trials. An assessment on second stage filter criteria ("equity", "strength of evidence", "feasibility" and "acceptability to stakeholders") is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are calculated for a period of one year for the eligible population (prevalent cases of generalized anxiety disorder/panic disorder identified in the National Survey of Mental Health and Wellbeing, extrapolated to the Australian population in the year 2000 for those aged 18 years and older). Simulation modelling techniques are used to present 95% uncertainty intervals (UI) around the incremental cost-effectiveness ratios (ICERs). RESULTS: Compared to current practice, CBT by a psychologist on a public salary is the most cost-effective intervention for both generalized anxiety disorder (A$6900/DALY saved; 95% UI A$4000 to A$12 000) and panic disorder (A$6800/DALY saved; 95% UI A$2900 to A$15 000). Cognitive behavioural therapy results in a greater total health benefit than the drug interventions for both anxiety disorders, although equity and feasibility concerns for CBT interventions are also greater. CONCLUSIONS: Cognitive behavioural therapy is the most effective and cost-effective intervention for generalized anxiety disorder and panic disorder. However, its implementation would require policy change to enable more widespread access to a sufficient number of trained therapists for the treatment of anxiety disorders.

Antidepressive Agents, Tricyclic↗

[Non-fearful panic disorder].

Panic disorder is among the most prevalent mental health disorders. Among other reasons, it is an important disorder due to its influence on all other medical professionals that these patients consult repeatedly. One of the major reasons for sub-optimal diagnosis is the different and less familiar presentations of the disorder. This article will focus on the "non-fearful" variant. Four case reports are described with prevalent presentations of the disorder and a summary of recommendations for better diagnosis of the disorder.

Adult↗

Psychotherapy for panic disorder.

Panic disorder is a common and debilitating illness in which unexpected panic episodes are the core feature. Medication treatment is of proven efficacy in this disorder. Cognitive behavioral treatment is also effective and can be administered without medication with good results. This paper reviews the techniques and strategies used in cognitive behavioral treatment and outcome results from studies utilizing this approach. The efficacy of other psychotherapeutic approaches is less well established. However, we recently conducted a study comparing cognitive behavioral treatment to an emotion focused brief psychotherapy and found them to be equivalent. We describe the theoretical background and the strategies and techniques for this treatment, and review the results of the prospective comparison.

Cognitive Behavioral Therapy↗

Respiratory feedback for treating panic disorder.

Panic disorder patients often complain of shortness of breath or other respiratory complaints, which has been used as evidence for both hyperventilation and false suffocation alarm theories of panic. Training patients to change their breathing patterns is a common intervention, but breathing rarely has been measured objectively in assessing the patient or monitoring therapy results. We report a new breathing training method that makes use of respiratory biofeedback to teach individuals to modify four respiratory characteristics: increased ventilation (Respiratory Rate x Tidal Volume), breath-to-breath irregularity in rate and depth, and chest breathing. As illustrated by a composite case, feedback of respiratory rate and end-tidal pCO2 can facilitate voluntary control of respiration and reduce symptoms. Respiratory monitoring may provide relevant diagnostic, prognostic, and outcome information.

Biofeedback, Psychology↗

Increased cholesterol levels after paroxetine treatment in patients with panic disorder.

Panic disorder (PD) is associated with an increased cardiovascular risk. We examined serum cholesterol and plasma catecholamine levels in PD before and after paroxetine treatment. The serum cholesterol and plasma catecholamine levels were not different between the PD patients and control subjects before the treatment. However, the levels of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were significantly increased in the 28 PD patients after 3 months of paroxetine treatment, whereas the body mass index and plasma catecholamine levels were unchanged. Paroxetine should be used cautiously for PD patients who have overt or covert cardiovascular disorders.

Adult↗