Drug Treatment Of Panic Disorder Research Articles

Participation of dorsal periaqueductal gray 5-HT1A receptors in the panicolytic-like effect of the κ-opioid receptor antagonist Nor-BNI

Panic patients may have abnormalities in serotonergic and opioidergic neurotransmission. The dorsal periaqueductal gray (dPAG) plays an important role in organizing proximal defense, related to panic attacks. The 5-HT1A receptor (5-HT1A-R) is involved in regulating escape behavior that is organized in the dPAG. Activation of κ-opioid receptor (KOR) in this region causes anxiogenic effects. In this study, we investigated the involvement of KOR in regulating escape behavior, using systemic and intra-dPAG injection of the KOR antagonist Nor-BNI. As panic models, we used the elevated T-maze (ETM) and the dPAG electrical stimulation test (EST). We also evaluated whether activation of the 5-HT1A-R or the μ-opioid receptor (MOR) in the dPAG contributes to the Nor-BNI effects. The results showed that systemic administration of Nor-BNI, either subcutaneously (2.0 and 4.0mg/kg) or intraperitoneally (2.0mg/kg), impaired escape in the EST, indicating a panicolytic-like effect. Intra-dPAG injection of this antagonist (6.8nmol) caused the same effect in the EST and in the ETM. Association of ineffective doses of Nor-BNI and the 5-HT1A-R agonist 8-OH-DPAT caused panicolytic-like effect in these two tests. Previous administration of the 5-HT1A-R antagonist WAY-100635, but not of the MOR antagonist CTOP, blocked the panicolytic-like effect of Nor-BNI. These results indicate that KOR enhances proximal defense in the dPAG through 5-HT1A-R modulation, independently of MOR. Because former results indicate that the 5-HT1A-R is involved in the antipanic action of antidepressants, KOR antagonists may be useful as adjunctive or alternative drug treatment of panic disorder.

Effect of Dissociative Experiences on Drug Treatment of Panic Disorder

Dissociative experiences are widespread among patients with panic disorder and have a negative impact on cognitive-behavioural therapy. In this study we aimed to investigate whether or not dissociative experiences affect response to drug treatment for panic disorder. Thirty-five patients, 20 women and 15 men, with a mean age of 35.4 years and a diagnosis of panic disorder, were enrolled in the study. Paroxetine 20 mg/day was administered over 6 weeks. Patients were assessed on the Dissociative Experience Scale (DES) and Panic and Agoraphobia Scale (PAS) at the commencement of therapy, and on the PAS again after therapy. The average DES score was determined as 30.3. Agoraphobia was identified in 34.3% of patients. DES scores were higher in patients with agoraphobia than in those without agoraphobia. Agoraphobia scores were higher in patients with high DES scores. When patients were divided into those with low DES scores (< or =30) and those with high DES scores (>30), a decrease in PAS scores with treatment was observed in both groups, but the decrease was greater in those with low DES scores (18.8 +/- 6.8 vs 5.7 +/- 5.7 in the high-DES score group; Z = 4.486, p = 0.00000053). Similarly, while a decrease in PAS scores with treatment was observed both in patients with agoraphobia (p < 0.05) and in those without agoraphobia, PAS scores decreased more in non-agoraphobic patients (16.7 +/- 7.5 vs 4.8 +/- 6.6 in patients with agoraphobia; Z = 3.799, p = 0.000047). In addition, the decrease in PAS scores was significantly correlated with baseline DES score (beta = 0.706, T = 5.727, p = 0.0000022). This study shows that dissociative experiences reduce the response to drug therapy in patients with panic disorder.

Developments in the drug treatment of panic disorder: What is the place of the selective serotonin reuptake inhibitors?

Panic disorder is becoming better recognised and understood as a chronic, debilitating but treatable condition. Drug treatment options shown by adequate research to be beneficial in this condition include mainly the benzodiazepine alprazolam, the tricyclic antidepressants (TCAs) imipramine and clomipramine, the monoamine oxidase inhibitor (MAOI) phenelzine, and the newer selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and paroxetine. Alprazolam, although approved for use in panic disorder in the US and very widely used, is associated with a risk of dependence and withdrawal syndromes. Given that depression frequently occurs as a comorbid condition with panic disorder the use of antidepressants is a logical choice. Among the antidepressants, MAOIs are little-used in panic disorder, mainly because of their potential for precipitating hypertensive crises if tyramine is ingested. TCAs are widely used and are effective but they are associated with initial activation, or ‘jitteriness’, have a 4–6-week time lag before onset of beneficial effect and produce troublesome side effects in a high proportion of patients, particularly during long-term use. TCAs are also cardiotoxic in overdosage, and panic disorder patients with comorbid depression are at high risk of attempted suicide. Serotonin dysregulation has been implicated in the pathogenesis of anxiety disorders in general, and panic disorder in particular. Among the TCAs, those with an effect on serotonin reuptake are most effective in panic disorder. SSRIs are specifically active on serotonin reuptake and do not have anticholinergic effects or act on the noradrenergic system. There is a clear pharmacological rationale for believing that SSRIs should be as effective as TCAs in panic disorder and better tolerated. Accumulating clinical research evidence supports this hypothesis. Further comparative studies with standard agents and additional long-term studies to support the initial long-term data with paroxetine are needed to confirm SSRIs as drug treatment of choice in panic disorder.

O-24-5 - Developments in the drug treatment of panic disorder

O-24-5 - Developments in the drug treatment of panic disorder

Developments in the drug treatment of panic disorder

Developments in the drug treatment of panic disorder

Differential Diagnosis and Drug Treatment of Panic Disorder, Anxiety and Depression

Depression and anxiety disorders are under-recognised in clinical practice. They are relatively common psychiatric disorders, affecting 2 to 5% of the population per year.

Long-term drug treatment of panic disorder

Drug treatment of panic disorder with benzodiazepines and antidepressants has been established as efficacious in the short-term (6–8 weeks). The efficacy of medications during long-term (i.e, continuous) treatment has not often been addressed and a review of the evidence is presented. Most data exists for the long-term effectiveness of benzodiazepines. Experience with the triazolobenzodiazepine, alprazolam, is reviewed together with some other high potency drugs, e.g, clonazepam. Tricyclic antidepressants are also effective in the long-term treatment of panic and the relevant studies are presented. Long-term efficacy for monoamine oxidase inhibitors is not as clearly established. The issue of relapse following drug withdrawal is addressed and some strategies for patient management in long-term therapy are discussed.

Drug treatment of panic disorder: early response to treatment as a predictor of final outcome

One of the core problems in clinical research is the detection of early changes in target symptoms that predict future therapeutic outcome. To analyze potential predictors of outcome, data of a multicenter study on patients with panic disorder were used. A total of 1010 patients were randomly allocated either to alprazolam, imipramine or placebo treatment. Early improvement in the number of spontaneous panic attacks within the first week of treatment predicted outcome exclusively in the alprazolam group. In contrast, placebo responders and nonresponders were differentiated by early changes in anticipatory anxiety intensity. For tricyclic antidepressants such as imipramine an evaluation period of more than one week is required to allow conclusions about outcome.

Drug Treatment of Panic Disorder

Drug Treatment of Panic Disorder

Drug treatment of panic disorder

Drug treatment of panic disorder

Long-term drug treatment of panic disorder

Long-term drug treatment of panic disorder