Dopaminergic challenges in social anxiety disorder: evidence for dopamine D3 desensitisation following successful treatment with serotonergic antidepressants.

Serotonergic antidepressants (SSRIs) are first-line treatments for social anxiety disorder [SAnD], though there is evidence of dopaminergic system dysfunction. Twenty subjects with DSM-IV SAnD, untreated (n = 10) and SSRI-remitted DSM-IV SAnD (n = 10), were administered a single dose of 1) a dopamine agonist (pramipexole 0.5 mg) and 2) a dopamine antagonist (sulpiride 400 mg), followed by anxiogenic challenges (verbal tasks and autobiographical scripts) in a double-blind crossover design, the two test days being one week apart. Anxiety symptoms were measured by self-reported changes in Visual Analogue Scales, specific SAnD scales and anxiety questionnaires. Plasma levels of prolactin were obtained. Untreated SAnD subjects experienced significant increases in anxiety symptoms following behavioural challenges after either sulpiride or pramipexole. Following remission with SSRIs, the socially anxiogenic effect of behavioural provocation was significantly attenuated under pramipexole, whereas under sulpiride effects remained significantly elevated. There appears to be instability of the dopamine system under behavioural stress in social anxiety subjects that is only partly rectified by successful treatment with an SSRI, which may induce a desensitisation of postsynaptic dopamine D(3) receptors.

Chest pain: panic attack or heart attack?

Chest pain is a common presentation to both primary and secondary care physicians but is often non-cardiac in origin. Patients presenting with chest pain may be experiencing a panic attack. Panic disorder is a disabling psychiatric condition with serious consequences, such as impaired social functioning and increased risk of suicide. Comorbidity of panic disorder with other psychiatric conditions is common and often leads to increased severity of anxiety symptoms and a poorer prognosis. The cost of misdiagnosing non-cardiac chest pain is high. It is important for physicians to be able to recognise panic attacks and to distinguish them from cardiac disease, thus avoiding unnecessary use of healthcare resources. This review discusses the prevalence and diagnosis of panic attack and panic disorder in patients presenting with chest pain to primary care physicians and cardiologists. Treatment options for panic disorder are considered, particularly the selective serotonin reuptake inhibitors, which are emerging as the first-line choice for the treatment of panic disorder.

Flumazenil challenge in social phobia.

The benzodiazepine antagonist, flumazenil, can provoke panic attacks in some panic disorder patients. It has been predicted that panic responses to flumazenil may be associated with situational fear. Patients with social phobia frequently experience situational anxiety and panic attacks. The current study tested whether flumazenil induces panic in patients with social phobia. Fourteen patients with social phobia (DSM-III-R) and 14 age- and sex-matched controls were tested in a single session, double blind crossover challenge design, using intravenous flumazenil 2 mg/20 ml or matched placebo infusions 1 hour apart. Panic attacks occurred during flumazenil challenge in 2/14 subjects with social phobia. The rate of panic attacks and the severity of panic symptoms following flumazenil were not significantly greater in patients than in controls. Situational fears that are provoked by social cues therefore do not predict panic responses to flumazenil.

Serotonin reuptake inhibitor withdrawal.

We studied reported withdrawal symptoms in a retrospective chart review of 352 patients treated in an outpatient clinic with the nonselective serotonin reuptake inhibitor clomipramine or with one of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine, paroxetine, or sertraline. In 171 patients who were supervised during medication tapering and discontinuation, the most common symptoms were dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood. When patients with at least one qualitatively new symptom were defined as cases, these symptoms occurred significantly more frequently in patients who had been treated either with one of the shorter half-life SSRIs, fluvoxamine or paroxetine (17.2%), or with clomipramine (30.8%), than in patients taking one of the SSRIs with longer half-life metabolites, sertraline or fluoxetine (1.5%). The rate was not significantly different between the different shorter half-life treatments. Cases treated with fluvoxamine or paroxetine had received a significantly longer period of treatment (median 28 weeks) than noncases (16 weeks), but there were no significant associations with age or with diagnostic grouping. There was a trend toward an association with male sex. The majority of cases occurred despite slowly tapered withdrawal. Symptoms persisted for up to 21 days (mean = 11.8 days) after onset. These symptoms were relieved within 24 hours by restarting the medication, but were not relieved by benzodiazepines or by moclobemide. A role has been suggested for serotonin in coordinating sensory and autonomic function with motor activity. We suggest that this may lead to useful hypotheses about the pathophysiology of withdrawal symptoms from serotonin reuptake inhibitors.

A comparison of the effects of phenelzine treatment with moclobemide treatment on cardiovascular reflexes.

The effects of treatment with phenelzine (n = 15) and moclobemide (n = 20) on heart rate variability and cardiovascular responses to standing were examined using non-invasive beat-to-beat blood pressure (BP) monitoring in an open cross-sectional study. Phenelzine markedly impaired the BP response compared with moclobemide, with 83% vs 15% of patients lacking the normal initial BP overshoot (p < 0.01). BP recovery to supine levels was delayed (median time for diastolic BP 14.5 s after phenelzine vs 4.9 s after moclobemide; p < 0.002). Standing BP at 1 min and its change from supine levels were also significantly lower in the phenelzine group (delta diastolic BP 4 mmHg vs 15 mmHg; p < 0.001). Heart rate responses and variability were preserved and did not differ between treatments. These findings are consistent with impairment of sympathetic function but preservation of parasympathetic responses after phenelzine treatment.