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A 51-year-old woman had panic disorder with agoraphobia and major depressive disorder sequentially. The aforementioned symptoms subsided significantly after treatment with milnacipran, 125 mg, administered daily for 2 months. However, panic attacks with agoraphobia were noted frequently when she tapered down milnacipran to 50 mg daily. She consequently experienced depression that gradually increased in degree, with poor energy, poor sleep, thoughts of helplessness, and ideas of death. After administration of a daily dose of 125 mg of milnacipran for 1 month, her panic attacks with agoraphobia and depressed mood were again alleviated. The present report shows significant effects of milnacipran on the comorbidity of panic disorder with agoraphobia and major depressive disorder.

Several anticonvulsants, although as yet not lamotrigine (LTG), have been found useful in the treatment of panic disorder with (PDA) or without agoraphobia. We administered LTG (200 mg/d) to 4 outpatients with PDA, as an augmentation therapy (3 patients with chronic and severe agoraphobia) or monotherapy (1 drug-naive patient with first-onset PDA) in a 14-week trial. The patient under LTG monotherapy improved significantly, whereas PDA symptoms in 2 of the other patients improved to some extent.

Objectives: Selective serotonin reuptake inhibitors (SSRIs) are currently considered as the first drug of choice in the treatment of panic disorder (PD). The aim of this long-term, naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD. Outcome measures included relapse rates and adverse effects., Methods: Two hundred patients with PD were enrolled in our study. All subjects met DSM-IV criteria for PD or PD with agoraphobia (PDA). All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram (n = 50), fluoxetine (n = 50), fluvoxamine (n = 50), or paroxetine (n = 50) in a randomized, nonblinded fashion. Both the treating psychiatrist and the patients were not blind to the assigned treatment, but the clinician raters were blind to the study medication. The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists. The Panic Self-Questionnaire, which is a self-report scale, was administered at baseline and then once per month during the duration of the 12-month study. The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study. Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits. The body weight of study subjects was measured at baseline, and then at the 12th month visit end point., Results: Of 200 patients who entered the study, 127 patients (63.5%) completed the full 12-month protocol. Retention rates were highest for paroxetine (76% [38/50]), intermediate for citalopram (68% [34/50]) and fluvoxamine (60% [30/50]), and lowest for fluoxetine (50% [25/50]). Patients who completed the 12-month protocol responded favorably to the study treatment. The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8. At visits on months 3, 6, 9, and 12, however, there were no statistically significant differences between the 4 groups in relapse rates (defined as the occurrence of 1 or more panic attacks during the previous week of treatment) (F1,127 = 0.17; P = 0.13 [not statistically significant]). At the 12th month end point, patients in all 4 treatment groups had a statistically significant increase in body weight. Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment. Reports of sexual adverse effects at the 12th month visit were similar in the citalopram, fluoxetine, and paroxetine groups, but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit., Conclusions: Most of our PD patients responded well to 12-month treatment with either citalopram, fluoxetine, fluvoxamine, or paroxetine, and the overall response rate was equal after the first 4 weeks of treatment. Although patients treated with paroxetine had the lowest dropout rates during the initiation phase, they had the highest rate of adverse effects as measured at the 12th month visit. Conversely, patients in the fluvoxamine group had the highest dropout rate (which was primarily caused by adverse effects in the initiation phase of treatment.); however, patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents. Overall, when measured at the 12th month visit, monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine. In addition, monotherapy with paroxetine, citalopram, and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine.

This study investigated the relationship between panic symptoms during remission and subsequent relapse of panic disorder. Research subjects were 169 individuals, enrolled in the Harvard/Brown Anxiety Research Project, who were in episodes of panic disorder at intake and remitted during the 8-year follow-up period. Panic symptoms during remission were examined as predictors of panic disorder relapse. For the relapses that did occur, we report the level of symptomatology during the previous 4 weeks. Depending on symptom severity and whether or not the relapse included agoraphobia, panic symptoms during remission were associated with an approximate two- to threefold increased risk of relapse. However, on examination of symptoms during the 4 weeks before relapse, we found that the majority of relapses were preceded by no panic symptoms. Thus, although panic symptoms during remission may indicate an increased risk of subsequent relapse, the absence of symptoms during remission does not indicate that relapse is unlikely.

We conducted a meta-analysis to update the knowledge of long-term efficacy of different treatments in panic disorder with or without agoraphobia. Included were 68 studies pertaining to 106 treatment conditions and 1346 patients. Effect sizes Cohen's d were calculated within the treatment conditions at posttest and at follow-up for panic and agoraphobia. A comparison was made between six treatments: high-potency benzodiazepines, antidepressants, psychological panic management, exposure in vivo, antidepressants combined with exposure, and psychological panic management combined with exposure in vivo. The mean (+/- SD) duration of the follow-up period was 62 +/- 89 weeks. In the majority of the studies (84%), follow-up had a naturalistic character. The lack of information about treatments received between posttest and follow-up limits the interpretation of the results. For all conditions, the treatment gains at posttest were maintained during the follow-up period. The mean (+/- SD) d for panic was 1.11 +/- 0.70 at posttest and 1.28 +/- 0.61 at follow-up; for agoraphobia, the mean d at posttest was 1.36 +/- 1.10 and at follow-up it was 1.41 +/- 0.82. Significant differences were found in efficacy on agoraphobic measures at follow-up between the combination of antidepressants and exposure in vivo versus psychological panic management, exposure in vivo, and the combination of psychological panic management and exposure. Overall, the data suggest that different treatment options for panic disorder with or without agoraphobia are effective at both posttest and follow-up. Research on long-term treatment, discontinuation of therapies, and interventions between posttest and follow-up need more attention, for pharmacotherapy as well as psychotherapy.

This review was designed to provide a detailed analysis of long-term outcome data from treatment studies for panic disorder, with the goal of ascertaining differential efficacy of the available treatments. Studies were included if they were published after 1980 and if follow-up took place at least 6 months after treatment termination. Thirty-one studies were located. A variety of methodological problems were found in these studies, including lack of clarity of diagnosis, lack of clarity in the treatment administered, and inadequately tracked nonstudy treatments during the study and follow-up periods, which limited the information that could be obtained about long-term outcome. Long-term outcome studies that closely track the additional treatments that patients receive are necessary to draw more definitive conclusions about differential treatment efficacy for panic disorder. Available data suggest that there is limited evidence for long-term maintenance of short-term treatment gains in panic disorder patients in the absence of continued treatment.

The objectives of this study were to a) replicate our prior finding of a decreased number (Bmax) of platelet alpha 2-adrenoreceptors in panic disorder, b) determine if binding is also decreased in asymptomatic first-degree relatives of panic patients (known to be at increased risk for developing panic), and c) evaluate the effect of treatment on the presumptive decrease in binding (i.e., is the decrease a state or a trait marker for panic?). Panic patients had clonidine and yohimbine platelet-binding assays, symptom ratings, and measurement of lying and standing plasma epinephrine, norepinephrine, systolic and diastolic blood pressure, and heart rate before treatment, after approximately 2 months of medication (fluoxetine, tricyclics, or alprazolam) and/or cognitive behavioral treatment, and after symptom remission while drug free; normal subjects had determinations of the same measures at approximately the same time intervals. Relatives of both groups had one determination only of all measures. Tritiated clonidine binding was decreased and lying heart rate was increased in patients before treatment. Magnitude of binding decrease was correlated with symptom severity and standing norepinephrine. No binding abnormality was seen in first-degree relatives of patients. Treatment increased clonidine binding in patients. Both patients and relatives of patients showed significantly increased standing plasma norepinephrine in comparison to controls. There is a state-related decrease in binding, associated with symptom severity and norepinephrine, in panic disorder. Abnormal reactivity of norepinephrine to standing might be a marker for increased likelihood of panic development in individuals at risk.

In an open-label pilot study, 35 outpatients with social phobia (DSM-III-R) received moclobemide for 12 weeks. The dosing range was 300-600 mg/day. Eighteen patients completed the study and 28 received at least 4 weeks of treatment. There was a consistent improvement in the efficacy parameters. Moclobemide was effective in both major components of social phobia (fear and avoidance). Moclobemide seems as effective as conventional irreversible monoamine oxidase inhibitors. Tolerability was good apart from one occurrence of grand mal seizure.

Monoamine oxidase (MAO) inhibitors are known to be effective in panic disorder, but a high incidence of adverse reactions have limited their use. The new, selective, and reversible MAO-A inhibitors exemplified by brofaromine and moclobemide do not require dietary restrictions, have fewer drug interactions, and are better tolerated. This paper reports a randomized, double-blind, 8-week trial in which the efficacy and safety of brofaromine was compared to clomipramine in patients with panic disorder with or without agoraphobia. Both treatments achieved a significant and comparable reduction in the number of panic attacks, and were equally effective in all the parameters measured. Side effects were typical of the drug class. Further trials are required to evaluate this promising new treatment.

In the psychiatric literature, panic attacks have been considered as part of the clinical manifestations of anxiety neurosis, agoraphobia, functional cardiovascular disturbances, and the phobic depersonalization syndrome. Even though recurrent spontaneous panic attacks are described in these entities, the importance ascribed to them has been minor one. Therefore, panic attacks are poorly understood from a psycho-physio pathological point of view. In the past years, new trends in the nosology of psychiatric disorders have grouped the recurrent spontaneous panic attacks under the heading "panic disorder and agoraphobia with panic attacks." In this view, we present the results of the controlled pharmacological trials on patients complaining of panic attacks. Some relationships between panic attacks, panic disorder, and agoraphobia are discussed.

This paper presents two sets of data that suggests a weak but specific placebo response in agoraphobia. First, analyses in 20 agoraphobic patients given single-blind placebo over a 2-week period, without the customary confound of instructions for exposure to phobic situations, revealed a statistically significant reduction in panic and phobic symptoms. However, symptoms remained in the moderate to severe range and functioning was virtually unchanged. Second, comparisons between six agoraphobic patients receiving double-blind placebo and six others receiving "no pills," matched for age, sex and exposure treatment, revealed a significant placebo effect over an 8-week period. Implications for clinical research are briefly discussed.

Ten cases are presented--two in detail--in which clonazepam was used successfully in patients with treatment-resistant panic disorder with or without agoraphobia. Seven of 10 patients who had been resistant to standard pharmacological treatments of panic attacks and agoraphobia achieved cessation of their attacks while three had mild to moderate symptom persistence. These data underscore other reports of clonazepam's usefulness in the treatment of panic disorder. Clinical use of clonazepam is discussed.

Agoraphobia, characterized as fear of going into public places, vehicles, shops, streets, and so forth, is a prevalent syndrome which permeates the patient's life. The efficacy of psychoanalytic, behavioral, and pharmacological treatments has been disappointing. The pervasive nature of agoraphobia dictates that its treatment is most efficacious when a combination of separate although interactive techniques is applied in concert. A multimodal behavioral conceptualization provides the vehicle for the systematic combined application of seemingly diverse individual approaches through monitoring and treating the BASIC ID, an acronym for behavior, affect, sensation, imagery, cognition, interpersonal relationships, and drugs. In an illustrative case, application of the multimodal behavioral conceptualization was instrumental in bringing relief to an agoraphobic patient's distress and disabilities.

Bupropion is a novel new antidepressant without the undesirable anticholinergic, cardiotoxic, sedative, or sexual side effects of other available antidepressants. However, like many other antidepressants, there is a small risk that patients on bupropion may develop a seizure even at moderate doses and moderate blood levels and even in the absence of any premorbid history or other predisposing factors to epilepsy. The report presents the case of a 25-year-old woman with a 12-year history of agoraphobia and panic attacks treated with bupropion in a research protocol. She was in good physical health, with normal physical and neurological examination, and normal complete blood count, serum mineral analysis-12, and urinalysis laboratory values. She had no premorbid history of epilepsy or neurological illness, nor any other known predisposing factors to epilepsy. On day 28 of the study, immediately after her dose of bupropion was increased from 450 to 600 mg/day, she had a generalized convulsion with tonic and clonic phases, loss of consciousness, and postictal confusion that was reliably witnessed by several observers. The EEG abnormality had cleared 15 days later. Further EEGs after 4 weeks and 10 weeks were normal. Five years later she remains seizure-free, off all antiseizure medication, and without any further complications from this incident. This seizure occurred at a modest blood level of bupropion (83 ng/ml) and at a dose not considered excessive (600 mg/day). Other confounding organic and neurological illness or use of other medication was carefully and systematically ruled out, leaving the bupropion as the most likely explanation for her seizure.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-seven patients participating in a controlled treatment study with imipramine were classified as high or low depressed simultaneously on two depression measures. Analysis of variance by 2 (high-low depressed) X 2 (high-low imipramine dosage) groupings revealed significant dose but no depression main effects. The greater dose effect observed in the low depressed group and the greater response rates found among high-dose patients with low initial depression strongly suggest that the beneficial effect of imipramine in agoraphobia was not primarily antidepressant in nature.

Five years after treatment in a controlled trial, in which all had received self-exposure homework, a group of 40 agoraphobic outpatients retained marked improvement in agoraphobia, mood, and free-floating anxiety. Frequency of spontaneous panics decreased as much in those who had placebo and self-exposure as in those who received imipramine and self-exposure. Few patients, however, were completely well at 5 years and over half had received further treatment for agoraphobia during the follow-up. Patients who were still highly phobic at the end of the clinical trial were more often prescribed psychotropic medication during follow-up and remained phobic at 5 years. Phobic improvement had generalized more in those patients with very low than in those with moderate pretreatment Hamilton depression scores. Frequency of initial spontaneous panics did not predict outcome. Improvement in agoraphobia was associated with improved marital adjustment. Those who began with the best marital, work, and social adjustment were more improved in their phobias 5 years later.