Renato T. Ramos

Clomipramine, a better reference drug for panic/agoraphobia. I. Effectiveness comparison with imipramine

An 8-week, double-blind, flexible-dose trial comparing low doses of clomipramine (mean=50 mg) with moderate doses of imipramine (mean=113.8 mg and propanteline (active placebo), was carried out in 60 out-patients with panic disorder with or without agoraphobia. Efficacy evaluation included global, anxiety and depression rating scales, and the determination of rates of relapse over up to 10 weeks of single-blind placebo follow-up. Both tricyclics were significantly more effective than propanteline, but clomipramine tended to act faster and more consistently than imipramine on most measures. Given the degree of blindness achieved and the significantly lower doses of clomipramine, this seems a better reference drug than imipramine for clinical trials in panic/agoraphobia.

Obsessive–compulsive symptoms in adults with history of rheumatic fever, Sydenham's chorea and type I diabetes mellitus: preliminary results

Objective:  Rheumatic fever (RF) associated with Sydenhams chorea (a neurological variant of RF), but not RF without chorea, has been acutely related to obsessive–compulsive symptomatology/disorder (OCS/OCD). This study investigated the presence of OCS in adults who had RF with or without chorea in childhood.

A dose-finding and discontinuation study of clomipramine in panic disorder

Eighty-one panic disorder patients with or without agoraphobia were treated with flexible doses of clomipramine under single-blind conditions. Fifty-seven (70.3%) reached operational criteria for full remission in 16.2 ± 6.5 weeks, with a mean dose of 89.1 ± 8.2 mg/day. Fifty-four (81%) of them received a continuous post-remission maintenance treatment at full doses of clomipramine for 4–6 months. No patient relapsed during the clomipramine maintenance phase. Their medication was then tappered and discontinued with placebo substitution under double-blind conditions. Fifty-one (63%) patients were followed-up until relapse or recurrence for up to 3 years, with periodic assessments. Three different outcome groups were identified: the first (n = 19, 19; 37.2%) experienced an early/immediate relapse (5.2 ± 4.9 weeks after drug discontinuation); the second group (n= 22, 22; 43.1%) experienced recurrence after 42.9 ± 35 weeks following discontinuation; and the third group (n = 10, 10; 19.6%) remained assymptomatic and functionally well throughout the follow-up. Predictors of early relapse were: (1) higher baseline score in the Beck Depression Inventory; (2) higher global score on the phobic avoidance scale after the full remission criteria; and (3) the need for higher clomipramine doses to reach full remission. The need for long-term or intermittent maintenance for most patients is emphasized.

Fear of heights: cognitive performance and postural control.

IntroductionFear of heights, or acrophobia, is one of the most frequent subtypes of specific phobia frequently associated to depression and other anxiety disorders. Previous evidence suggests a correlation between acrophobia and abnormalities in balance control, particularly involving the use of visual information to keep postural stability. This study investigates the hypotheses that (1) abnormalities in balance control are more frequent in individuals with acrophobia even when not exposed to heights, that (2) acrophobic symptoms are associated to abnormalities in visual perception of movement; and that (3) individuals with acrophobia are more sensitive to balance-cognition interactions.MethodThirty-one individuals with specific phobia of heights and thirty one non-phobic controls were compared using dynamic posturography and a manual tracking task.ResultsAcrophobics had poorer performance in both tasks, especially when carried out simultaneously. Previously described interference between posture control and cognitive activity seems to play a major role in these individuals.DiscussionThe presence of physiologic abnormalities is compatible with the hypothesis of a non-associative acquisition of fear of heights, i.e., not associated to previous traumatic events or other learning experiences. Clinically, this preliminary study corroborates the hypothesis that vestibular physical therapy can be particularly useful in treating individuals with fear of heights.

Balance disturbances in asthmatic patients.

Objective. The aim of this study was to investigate balance control in asthmatic patients. Methods. Thirty subjects with controlled persistent asthma were compared with 30 non-asthmatic subjects who were matched by age and sex. Individuals who had received psychiatric treatment, demonstrated chronic musculoskeletal pain, had limited joint movements, or showed vestibular or other equilibrium disorders were excluded from both the groups to avoid biomechanical bias in the dynamic posturography. Balance control was evaluated with the subject standing still on a force platform under four different sensory test conditions. These conditions combined the subject’s eyes being opened or closed with a fixed or mobile force platform. A mobile platform provides a somatosensory perturbation, and when associated with the eyes closed condition, only vestibular information is available to moderate balance control. Sensory manipulation provides a more sensitive condition to differentiate postural control between populations or pathologies. Data were sampled at 100 Hz in three 20-second trials and four postural conditions were assessed. The center of pressure (CoP) displacement values were used to calculate area and velocity in the medial–lateral and forward–backward directions. A two-factor analysis of variance with repeated measurements was applied to the data. Results. In comparison to the control group, the asthma group demonstrated a greater area of CoP displacement in conditions using the mobile force platform (with eyes opened or closed) and a higher velocity in forward–backward direction on the mobile platform with the eyes closed. Conclusion. Asthmatic individuals presented a greater area for the CoP displacement under somatosensory perturbations and a higher velocity in the forward–backward direction when vestibular information only was made available. Our data suggest that balance needs to be evaluated in asthmatic patients.

Antidepressants and dizziness

Despite several evidences supporting a close relationship between dizziness and anxiety symptoms, the role of antidepressants in the treatment of such conditions remains poorly explored. The high prevalence of dizziness during serotonin reuptake inhibitors discontinuation syndrome and the few reports suggesting efficacy of antidepressants in treating some vestibular disorders justify a careful investigation. Neurophysiologic studies suggest possible focus of investigation on mechanisms of drug action. Psychophysiologic studies also suggest a possible role of antidepressant drugs in improving balance control and cognitive functioning. Controlled studies involving antidepressants with selective action in different neurotransmitters systems are necessary to elucidate the complex pathophysiologic mechanisms involving emotional and balance control. For future researches, special attention must be paid to the methodology of balance evaluation and the interaction between posture control and cognitive functioning.

Minor and Unsystematic Cortical Topographic Changes of Attention Correlates between Modalities

In this study we analyzed the topography of induced cortical oscillations in 20 healthy individuals performing simple attention tasks. We were interested in qualitatively replicating our recent findings on the localization of attention-induced beta bands during a visual task [1], and verifying whether significant topographic changes would follow the change of attention to the auditory modality. We computed corrected latency averaging of each induced frequency bands, and modeled their generators by current density reconstruction with Lp-norm minimization. We quantified topographic similarity between conditions by an analysis of correlations, whereas the inter-modality significant differences in attention correlates were illustrated in each individual case. We replicated the qualitative result of highly idiosyncratic topography of attention-related activity to individuals, manifested both in the beta bands, and previously studied slow potential distributions [2]. Visual inspection of both scalp potentials and distribution of cortical currents showed minor changes in attention-related bands with respect to modality, as compared to the theta and delta bands, known to be major contributors to the sensory-related potentials. Quantitative results agreed with visual inspection, supporting to the conclusion that attention-related activity does not change much between modalities, and whatever individual changes do occur, they are not systematic in cortical localization across subjects. We discuss our results, combined with results from other studies that present individual data, with respect to the function of cortical association areas.

Space and motion discomfort in Brazilian versus American patients with anxiety disorders.

Space and motion discomfort (SMD) was studied in 38 Brazilian and 50 U.S. patients belonging to one of three diagnostic groups: (a) panic disorder with agoraphobia, (b) panic disorder without agoraphobia, and (3) other nonpanic anxiety disorders. A group of 30 U.S. normal controls was also included. SMD was assessed by the Situational Characteristics Questionnaire (SitQ), which includes two scales for SMD--the Smd1 and the Smd2, and one scale for non-space-related agoraphobic discomfort, the Ag1. The score in the Smd2 is based on the sum of Likert style items, while the scores of the Smd1 and Ag1 are based on differences between contrasting subitems. A significant diagnosis effect was observed in all scales, with the highest scores in the agoraphobia group. A country effect was found only in the Smd2. A country effect was also observed when all subitems of the Smd1 and Ag1 were added rather than subtracted, suggesting that this country bias is related to a tendency of Brazilian patients to endorse symptoms. Implications of these findings to the trans-cultural validation of rating scales are discussed.

Panic disorder patients have reduced cyclic AMP in platelets

Little is known about the intracellular mechanisms involved in the pathophysiology of panic disorder (PD). Abnormalities in the cyclic AMP system have been described in several psychiatric disorders but there are no studies in panic patients. We evaluated not only the levels of platelet cyclic AMP, but also cyclic GMP and nitric oxide synthase (NOS) activity in patients with PD at baseline and after treatment with clomipramine and in healthy volunteers. Platelet cyclic AMP was determined by enzymeimmunoassay, cyclic GMP by radioimmunoassay and NOS activity by the conversion of (3)H-arginine to (3)H-citruline in 17 PD patients before treatment with clomipramine, after remission of panic attacks and in 22 healthy volunteers. Average baseline cyclic AMP of PD patients was lower than after remission of panic attacks (P<0.005) and lower than in healthy volunteers (P<0.005). Average cyclic AMP after remission of panic attacks was not significantly different than in healthy volunteers. There were no significant differences in cyclic GMP and NOS analysis. Our results suggest that PD patients without treatment have lower platelets cyclic AMP levels than healthy volunteers and that this decrease may be corrected by clomipramine.

Precueing time but not direction of postural perturbation induces early muscular activation: comparison between young and elderly individuals.

In this study, we evaluated the effect of precueing characteristics of an impending perturbation to upright stance on reactive responses of distal leg muscles. Young and older individuals were compared in a task of recovering stable upright stance following rotation of the supporting platform to induce anterior or posterior body sway. Directions of the supporting platform rotation were randomized across trials. Immediately before postural perturbation participants were cued about direction and/or time of platform rotation, or performed the task under directional and temporal uncertainty of the impending perturbation. Results showed that precueing time of perturbation led to earlier muscular activation onset, while precueing perturbation direction did not modulate either latency or magnitude of muscular activation. Those effects were similar between age groups. Our findings suggest that awareness of the perturbation time favored shorter response latencies in both the young and older individuals.