Symptoms and physiologic manifestations in obsessive compulsive patients before and after treatment with clomipramine.

BACKGROUND: Anxiety and hyperarousal constitute important aspects of obsessive compulsive disorder (OCD). This study examined the effects of clomipramine on symptoms, arousal-related physiologic states, and stress reactions in OCD patients. METHOD: Twenty-five OCD patients were randomly assigned to a clomipramine or placebo group and were assessed for 10 weeks using a double-blind parallel design. They were assessed clinically with the Yale-Brown Obsessive Compulsive Scale, the National Institute of Mental Health Global Obsessive-Compulsive Scale, the patient- and investigator-rated Global Improvement Scales, and the Hamilton Rating Scale for Depression. Prior to treatment, and again during the last day of medication, physiologic states (heart rate, respiration, skin conductance, blood pressure, and EMG) were measured at rest and during both nonspecific (psychomotor tasks) and pathology-specific (visualization) stressors. RESULTS: Patients taking clomipramine, but not those taking placebo, improved significantly on all clinical measures. With the exception of heart rate, treatment did not affect resting physiologic states. Heart rate increased in patients taking clomipramine and decreased in patients taking placebo. Autonomic reactivity to nonspecific and to pathology-specific stressors was attenuated by clomipramine, but not by placebo. CONCLUSION: Clinical improvement on clomipramine treatment was independent of the physiologic state of the patients and was not associated with autonomic down-regulation. The attenuation of autonomic reactivity to stressors appears not to be pathology-specific but may reflect either a direct pharmacologic effect of clomipramine on the autonomic nervous system or a heightened indifference to psychological stressors in general.

Effects of alprazolam and imipramine on parasympathetic cardiac control in patients with generalized anxiety disorder.

A noninvasive measure was used to assess the effects of alprazolam, imipramine and placebo on parasympathetic (vagal) cardiac control following 6-weeks of medication in patients with generalized anxiety disorder. Flexible dosage at therapeutic levels resulted in increased heart rate and blood pressure and in decreased cardiac vagal control in patients receiving imipramine but not alprazolam or placebo. About 50% of the variance in heart rate changes and changes in mean arterial blood pressure following treatment with imipramine could be accounted for by changes in cardiac vagal control. Decreased cardiac vagal control can now be added to the list of cardiovascular changes seen following several weeks of treatment with imipramine.

Psychophysiological response patterns in panic disorder.

To determine whether panic disorder patients exhibit physiological hyperarousal during rest or during mild, non-panic-inducing stress, 18 patients who experienced frequent panic attacks were compared with nonanxious controls on a battery of physiological assessments. During baseline, patients with panic disorder exhibited higher forehead electromyographic activity, higher systolic blood pressure and higher heart rates than non-anxious volunteers. During psychological stress, heart rate and systolic blood pressure rose more in patients with panic disorder than in nonanxious controls. The skin conductance response, however, was greater and more variable in the nonanxious controls. The results suggest that panic disorder patients with frequent panic attacks exhibit heightened cardiovascular arousal and decreased electrodermal flexibility than nonanxious people, even in nonthreatening situations.

Treatment effects of alprazolam and imipramine: physiological versus subjective changes in patients with generalized anxiety disorder.

The correspondence between changes in physiological activity and somatic symptom reports was assessed in generalized anxiety disorder patients treated with alprazolam or imipramine. After 6 weeks, the two medications produced comparable reductions in self-reported somatic symptoms. However, patients taking alprazolam showed decreases in systolic blood pressure, epinephrine, and norepinephrine, and patients taking imipramine showed increases in heart rate, blood pressure, electromyographic activity, and norepinephrine. Thus, though the physiological changes associated with alprazolam treatment were consistent with changes in symptom reports, treatment with imipramine produced a desynchrony: patients reported significant decreases in cardiovascular symptoms and muscle tension in spite of the fact that heart rate, blood pressure, and electromyographic activity increased. Possible explanations for this counterintuitive phenomenon are discussed.

Somatic manifestations in women with generalized anxiety disorder. Psychophysiological responses to psychological stress.

Generalized anxiety disorder is associated with symptoms that suggest heightened muscular tension and autonomic arousal. Since self-reports of physiological states in patients with anxiety disorder are frequently unreliable, we compared 20 female patients with generalized anxiety disorder with a matched group of nonanxious controls on a battery of psychophysiological assessments (skin conductance, heart interbeat interval, blood pressure, respiration, and forehead and gastrocnemius electromyographic activity). We found that during baseline patients with generalized anxiety disorder differed from controls on electromyographic, but not on autonomic, measures. During psychological stress tasks, patients with generalized anxiety disorder showed a weaker mean skin conductance response with a narrower range in both skin conductance and heart rate than controls. These findings suggest that sympathetic inhibition, rather than enhancement, occurs in patients with generalized anxiety disorder during performance stress.

Symptoms and treatment responses of generalized anxiety disorder patients with high versus low levels of cardiovascular complaints.

Clinical observations suggest that patients with generalized anxiety disorder differ in somatic symptoms. The authors compared 28 patients with generalized anxiety disorder who had high levels of cardiovascular complaints with 32 patients with generalized anxiety disorder who had low levels of cardiovascular complaints on rating instruments, physiological measures, and use of anxiolytic medication. The two groups differed on somatic but not psychic symptoms on rating instruments. Patients with high levels of cardiovascular symptoms had higher levels of cardiac lability and required higher doses of alprazolam. These findings suggest that anxious patients with comparable levels of psychic anxiety may differ in levels of physical symptoms.

Differential effects of alprazolam and imipramine in generalized anxiety disorder: somatic versus psychic symptoms.

Some researchers have recently suggested that antidepressants may be superior to benzodiazepines in the alleviation of generalized anxiety. In a 6-week, double-blind, parallel-design study with flexible dosage scheduling, the authors compared the effects of alprazolam with those of imipramine in 60 patients who had generalized anxiety disorder. On rating scales that contained both psychic and somatic symptoms, patients in both treatment groups improved to a similar degree after 2 weeks. However, alprazolam was more effective in attenuating somatic symptoms, and imipramine was more effective in attenuating psychic symptoms such as dysphoria and negative anticipatory thinking. The authors' results suggest that, in generalized anxiety, somatic symptoms and hyperarousal selectively respond to drugs acting on the gamma-aminobutyric acid system, whereas psychic symptoms respond to treatments affecting the noradrenergic or serotonergic systems.