Comparison of aerobic exercise, clomipramine, and placebo in the treatment of panic disorder.

OBJECTIVE: The purpose of this study was to compare the therapeutic effect of exercise for patients with panic disorder to a drug treatment of proven efficacy and to placebo. METHOD: Forty-six outpatients suffering from moderate to severe panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to a 10-week treatment protocol of regular aerobic exercise (running), clomipramine (112.5 mg/day), or placebo pills. RESULTS: The dropout rate was 31% for the exercise group, 27% for the placebo group, and 0% for the clomipramine group. In comparison with placebo, both exercise and clomipramine led to a significant decrease in symptoms according to all main efficacy measures (analysis of variance, last-observation-carried-forward method and completer analysis). A direct comparison of exercise and clomipramine revealed that the drug treatment improved anxiety symptoms significantly earlier and more effectively. Depressive symptoms were also significantly improved by exercise and clomipramine treatment. CONCLUSIONS: These results suggest that regular aerobic exercise alone, in comparison with placebo, is associated with significant clinical improvement in patients suffering from panic disorder, but that it is less effective than treatment with clomipramine.

Decreased neuroendocrine responses to meta-chlorophenylpiperazine (m-CPP) but normal responses to ipsapirone in marathon runners.

Several clinical studies suggest antidepressive and anxiolytic effects of regular aerobic exercise. To study the effects of exercise on central serotonergic receptor sensitivity, we performed neuroendocrine challenges using oral doses of meta-chlorophenylpiperazine (m-CPP, 0.4 mg/kg), ipsapirone (0.3 mg/kg) and placebo in 12 marathon runners and 12 healthy controls not practicing regular exercise. After administration of the nonselective serotonergic agonist m-CPP, which exerts a number of well-reproducible effects mainly by means of its action on 5-HT2C receptors, marathon runners showed a significantly reduced cortisol response in comparison to the control group. There was also a statistical trend toward a blunted prolactin response after m-CPP in the athlete group. In contrast, the increase of cortisol and the hypothermia observed after administration of the 5-HT1A agonist ipsapirone were of the same magnitude in both groups. The behavioral response to m-CPP or ipsapirone and the mean maximal increases of plasma adrenaline and noradrenaline did not differ between the marathon and the control group. In conclusion, exercise-induced downregulation of 5-HT2C receptors could play an important role in mediating the anxiolytic and antidepressive effects of exercise.

Effect of aerobic exercise on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine and to ipsapirone in untrained healthy subjects.

RATIONALE: Several clinical studies suggest antidepressive and anxiolytic effects of regular aerobic exercise. OBJECTIVES: The present study examines the effects of a 10-week protocol of moderate aerobic exercise (3-4 miles jogging 3 times per week) on central serotonergic receptor sensitivity. METHODS: Neuroendocrine challenges using oral doses of meta-chlorophenylpiperazine (m-CPP; 0.4 mg/kg), ipsapirone (0.3 mg/kg), and placebo were performed in 12 untrained healthy volunteers before and after 10 weeks of moderate aerobic exercise. RESULTS: Before training, administration of the non-selective serotonergic agonist m-CPP, which exerts a number of well-reproducible effects mainly via its action on 5-HT2C receptors, was associated with a significant increase of cortisol and prolactin (but not adrenaline or noradrenaline) in comparison with the placebo condition. After the 10-week training period, administration of m-CPP was followed by a blunted cortisol response which was not significantly increased in comparison to the placebo challenge. In contrast, the increases of cortisol observed after administration of the 5-HT1A agonist ipsapirone were of the same magnitude during the pre- and post-training challenge sessions. The behavioral response to ipsapirone and the mean maximal increases of plasma adrenaline and noradrenaline did not change during the training period. CONCLUSIONS: Regular aerobic exercise is associated with a blunted cortisol response to m-CPP, which might reflect a downregulation of central 5-HT2C receptors.

5-HT1A responsivity in patients with panic disorder before and after treatment with aerobic exercise, clomipramine or placebo.

Blunted neuroendocrine and physiological responses to the selective 5-HT(1A) receptor agonist, ipsapirone, have been observed in patients with panic disorder and/or agoraphobia (PDA). In order to examine whether this hyporesponsiveness to ipsapirone is modified by pharmacological or non-pharmacological therapeutic interventions, challenges with an oral dose of ipsapirone (0.3 mg/kg) and placebo were performed in patients with PDA before and after 10 weeks of treatment with clomipramine, aerobic exercise and placebo. Before treatment, administration of ipsapirone was followed by significant increases of cortisol, anxiety and other psychopathological symptoms in comparison to the placebo challenge. In addition, a significant decrease of body temperature was observed. After the 10-week treatment period, the psychological responses to ipsapirone were significantly reduced in the clomipramine and the exercise group. In contrast, there was a non-significant trend towards higher cortisol responses after clomipramine and exercise treatment. The hypothermic response to ipsapirone was significantly reduced by clomipramine treatment. In conclusion, our results demonstrate that effective treatment of panic disorder has divergent effects on the psychological, neuroendocrine and temperature responses to ipsapirone.

Endurance training in panic patients: spiroergometric and clinical effects.

Endurance capacity was determined by bicycle spiroergometry in patients with panic disorder before (n = 38) and after (n = 10) a 10 week running program and compared to untrained healthy control subjects carrying out the same training (n = 11) and patients receiving clomipramine drug therapy (n = 7) or placebo (n = 7). Before the running program maximal oxygen uptake (VO2peak) and the workload corresponding to a lactate concentration of 4 mmol/l (PLAC4) were significantly reduced in panic patients compared to controls. Patients in the running program and healthy controls improved PLaC4 significantly by running. No significant differences in endurance gains were found between these groups, showing that patients and controls improved equally. At study termination (week 10) running was more efficient than placebo in improving panic symptoms (Bandelow PanicAgoraphobia Scale, Hamilton Anxiety Scale, Clinical Global Impression Scale). Clomipramine treatment was better than placebo (all scales) and running (only Clinical Global Impression). Endurance capacity did not correlate with anxiety scores at baseline, nor did improvement in fitness substantially correlate with changes in psychopathology measures during the study. Panic patients were shown to have a decreased endurance capacity which can be raised by training. Endurance training based on spiroergometric results gives rise to clinical improvement.

Exercise avoidance and impaired endurance capacity in patients with panic disorder.

Exercise habits and indices of aerobic fitness as measured by spiroergometric testing were examined in 38 patients with panic disorder and/or agoraphobia and 24 untrained healthy controls. Maximal oxygen consumption, maximal power output and the power output at a lactate concentration of 4 mmol/l were significantly reduced in the patient group when compared to untrained controls. Other parameters like physical work capacity at a heart rate of 150/min, maximal lactate concentration, vital capacity, subjective exertion at maximal work load, and maximal heart rate did not differ between patients and controls. Patient interviews revealed that aerobic exercise is avoided by the vast majority of patients. Reduced aerobic fitness might contribute to the pathophysiology of panic disorder and/or agoraphobia.

[Value of sports in treatment of psychiatric illness]. / Zum Stellenwert von Sport in der Behandlung psychischer Erkrankungen.

Several studies in healthy volunteers have shown a positive effect of endurance training on anxiety, depressive symptoms, self-esteem, concentration and stress tolerance. There are only a few controlled studies examining the therapeutic potential of exercise in psychiatric disorders. However, there is good evidence that exercise is effective in mild to moderate depression and in anxiety disorders. The therapeutic effect did not correlate with changes in cardiopulmonary fitness in the majority of studies. Therefore, other neurobiological and psychological mechanisms are discussed which might explain the effectiveness of regular physical training. The authors offer a variety of suggestions, how exercise could be integrated and evaluated in the treatment of psychiatric disorders.

The use of the Panic and Agoraphobia Scale (P & A) in a controlled clinical trial.

BACKGROUND: A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia, the Panic and Agoraphobia Scale (P & A). The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients (panic attacks, avoidance, anticipatory anxiety, disability and worries about health). The application of this scale in a double-blind placebo-controlled panic disorder trial is described. At the same time, the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy. METHODS: Patients with Panic disorder (DSM-IV) were randomly assigned to three treatment modalities: running (n=45), clomipramine (n=15) or placebo (n=15). Treatment efficacy was measured with the Panic and Agoraphobia Scale (P & A) and other rating scales. RESULTS: According to the P & A and other scales, both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment. Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise. The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability. CONCLUSIONS: The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments. Analysis of the scales five subscores may help to understand mechanisms of action of panic disorder treatments.