Pharmacotherapy Of Panic Disorder Research Articles

P.0643 Anticonvulsant and antipsychotic medications in the pharmacotherapy of panic disorder: an updated review

P.0643 Anticonvulsant and antipsychotic medications in the pharmacotherapy of panic disorder: an updated review

Anticonvulsant and antipsychotic medications in the pharmacotherapy of panic disorder: a structured review

Background:As the remission rate of panic disorder (PD) achieved with conventional pharmacotherapy ranges between 20% and 50%, alternative psychopharmacological strategies are needed. We aimed to firstly review data regarding use of antipsychotic and non-benzodiazepine anticonvulsant medication in PD patients with or without comorbidities; secondly, to review data concerning reduction of panic symptoms during treatment of another psychiatric disorder with the same medications; and thirdly, to examine reports of anticonvulsant- or antipsychotic-induced new-onset panic symptomatology.Methods:We performed a PubMed search (last day: 28 April 2020) of English-language studies only, combining psychopathological terms (e.g. ‘panic disorder’) and terms referring either to categories of psychotropic medications (e.g. ‘anticonvulsants’) or to specific drugs (e.g. ‘carbamazepine’). All duplications were eliminated. All studies included in the review met certain inclusion/exclusion criteria. The level of evidence for the efficacy of each drug was defined according to widely accepted criteria.Results:In treatment-resistant PD, beneficial effects have been reported after treatment (mostly augmentation therapy) with a range of anticonvulsant (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbamazepine, valproate, vigabatrin, tiagabine) and antipsychotic (aripiprazole, olanzapine, risperidone, sulpiride) medications: overall, most medications appear generally well tolerated. Additionally, bipolar patients receiving valproate or quetiapine-XR (but not risperidone or ziprasidone) demonstrated reductions of comorbid panic-related symptoms. There are case reports of new-onset panic symptoms associated with clozapine, haloperidol, olanzapine and topiramate, in patients with conditions other than PD. The small-to-modest sample size, the lack of control groups and the open-label and short-term nature of most of the reviewed studies hinder definitive conclusions regarding either the short-term and long-term efficacy of antipsychotic and anticonvulsant medications or their potential long-term side effects.Conclusion:Some atypical antipsychotic and anticonvulsant medications may have a role in the treatment of some PD patients, mostly when more conventional approaches have not been successful, but the quality of supporting evidence is limited.

Pharmacological Therapy in Panic Disorder: Current Guidelines and Novel Drugs Discovery for Treatment-resistant Patient.

Panic disorder (PD) being one of the most intensively investigated anxiety disorders is considered a heterogeneous psychiatric disease which has difficulties with early diagnosis. The disorder is recurrent and usually associated with low remission rates and high rates of relapse which may exacerbated social and quality of life, causes unnecessary cost and increased risk for complication and suicide. Current pharmacotherapy for PD are available but these drugs have slow therapeutic onset, several side effects and most patients do not fully respond to these standard pharmacological treatments. Ongoing investigations indicate the need for new and promising agents for the treatment of PD. This article will cover the importance of immediate and proper treatment, the gap in the current management of PD with special emphasis on pharmacotherapy, and evidence regarding the novel anti-panic drugs including the drugs in developments such as metabotropic glutamate (mGlu 2/3) agonist and levetiracetam. Preliminary results suggest the anti-panic properties and the efficacy of duloxetine, reboxetine, mirtazapine, nefazodone, risperidone and inositol as a monotherapy drug. Apart for their effectiveness, the aforementioned compounds were generally well tolerated compared to the standard available pharmacotherapy drugs, indicating their potential therapeutic usefulness for ambivalent and hypervigilance patient. Further strong clinical trials will provide an ample support to these novel compounds as an alternative monotherapy for PD treatment-resistant patient.

Neonatal outcomes in pregnant women with untreated and treated panic disorder

ObjectiveThe objective of the present study was to compare neonatal outcomes including gestational age, birth weight and hospitalization of newborns of pregnant women with treated with antidepressants and untreated panic disorder. MethodsThe study sample included 146 pregnant women (44 patients with panic disorder treated with antidepressants, 52 patients with untreated panic disorder, and 50 healthy controls). Panic disorder was diagnosed by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. ResultsThe highest proportions of preterm birth (28.8%), low birth weight (34.6%) and requirement of neonatal care (25.0%) were observed in infants of untreated patients. Pharmacotherapy group and control subjects had similar neonatal outcomes. Compared with infants of healthy subjects and the pharmacotherapy group, infants of untreated patients had significantly lower birth weight and gestational age at delivery. In addition, newborns of untreated patients had higher rate of hospitalization at the neonatal care unit. ConclusionOur results suggest that treatment with pharmacotherapy of panic disorder during pregnancy may have beneficial effects on the risk of negative neonatal outcomes due to maternal panic disorder in the infants.

Personalized medicine in panic disorder: where are we now? A meta-regression analysis

Personalized medicine assumes that individual’s unique characteristics are central in tailoring effective pharmacological interventions. The identification of predictors of pharmacotherapy effectiveness is crucial in panic disorder (PD), but consensus on this topic is still lacking. Consequently, we carried out a meta-analysis, according to PRISMA guidelines, with the aim of identifying sociodemographic and clinical moderators of short-term outcomes and tolerability of US FDA-approved medications for PD. We performed a database search on randomized placebo-controlled trials using PubMed, PsycINFO, and Embase. Through the selection process, we finally meta-analyzed 29 comparisons between paroxetine, venlafaxine XR or alprazolam and placebo. We employed the random-effects meta-regression technique. The major results were that longer illness duration was significantly associated with a lower rate of patients free from panic attacks at the end of trials with venlafaxine XR, and that higher age at the beginning of trials was significantly associated with a higher rate of dropouts because of side effects during trials with paroxetine. In addition, longer treatment was associated with a higher rate of patients free from panic attacks at endpoint in trials with venlafaxine XR. Overall, we found limited support for the moderating effects of sociodemographic and clinical variables on the short-term pharmacotherapy for PD. However, our results should be considered with caution considering the limited statistical power and the risk of publication bias. Future studies are needed to overcome the paucity of available data and the shortcoming of the current pharmacological studies in PD.

Is There Room for Second-Generation Antipsychotics in the Pharmacotherapy of Panic Disorder? A Systematic Review Based on PRISMA Guidelines.

A role for second-generation antipsychotics (SGAs) in the treatment of panic disorders (PD) has been proposed, but the actual usefulness of SGAs in this disorder is unclear. According to the PRISMA guidelines, we undertook an updated systematic review of all of the studies that have examined, in randomized controlled trials, the efficacy and tolerability of SGAs (as either monotherapy or augmentation) in the treatment of PD, with or without other comorbid psychiatric disorders. Studies until 31 December 2015 were identified through PubMed, PsycINFO, Embase, Cochrane Library and Clinical trials.gov. Among 210 studies, five were included (two involving patients with a principal diagnosis of PD and three involving patients with bipolar disorder with comorbid PD or generalized anxiety disorder). All were eight-week trials and involved treatments with quetiapine extended release, risperidone and ziprasidone. Overall, a general lack of efficacy of SGAs on panic symptoms was observed. Some preliminary indications of the antipanic effectiveness of risperidone are insufficient to support its use in PD, primarily due to major limitations of the study. However, several methodological limitations may have negatively affected all of these studies, decreasing the validity of the results and making it difficult to draw reliable conclusions. Except for ziprasidone, SGAs were well tolerated in these short-term trials.

Facing the fear – clinical and neural effects of cognitive behavioural and pharmacotherapy in panic disorder with agoraphobia

Introduction: Cognitive behavioural therapy (CBT) and pharmacological treatment with selective serotonin or serotonin-noradrenalin reuptake inhibitors (SSRI/SSNRI) are regarded as efficacious treatments for panic disorder with agoraphobia (PD/AG). However, little is known about treatment-specific effects on symptoms and neurofunctional correlates. Experimental procedures: We used a comparative design with PD/AG patients receiving either two types of CBT (therapist-guided (n=29) or non-guided exposure (n=22)) or pharmacological treatment (SSRI/SSNRI; n=28) as well as a wait-list control group (WL; n=15) to investigate differential treatment effects in general aspects of fear and depression (Hamilton Anxiety Rating Scale HAM-A and Beck Depression Inventory BDI), disorder-specific symptoms (Mobility Inventory MI, Panic and Agoraphobia Scale subscale panic attacks PAS-panic, Anxiety Sensitivity Index ASI, rating of agoraphobic stimuli) and neurofunctional substrates during symptom provocation (Westphal-Paradigm) using functional magnetic resonance imaging (fMRI). Comparisons of neural activation patterns also included healthy controls (n=29). Results: Both treatments led to a significantly greater reduction in panic attacks, depression and general anxiety than the WL group. The CBT groups, in particular, the therapist-guided arm, had a significantly greater decrease in avoidance, fear of phobic situations and anxiety symptoms and reduction in bilateral amygdala activation while the processing of agoraphobia-related pictures compared to the SSRI/SSNRI and WL groups. Discussion: This study demonstrates that therapist-guided CBT leads to a more pronounced short-term impact on agoraphobic psychopathology and supports the assumption of the amygdala as a central structure in a complex fear processing system as well as the amygdala׳s involvement in the fear system׳s sensitivity to treatment.

Bupropion and Panic Disorder: Case Report and Review of the Literature

Bupropion and Panic Disorder: Case Report and Review of the Literature

Platelet serotonin transporter function after short-term paroxetine treatment in patients with panic disorder

Dysfunctions in serotonin neurotransmission have been implicated in some psychiatric disorders, and in particular, altered serotonin transporter function has been noted in panic disorder. In this study, the authors compared platelet [ 3H]serotonin uptake parameters, including maximum velocities ( V max) and affinity constants ( K m), in patients with panic disorder not undergoing treatment ( n = 21) and in healthy subjects ( n = 20). V max and K m values were re-examined after 12 weeks of paroxetine treatment. Values of V max and K m were lower in panic disorder patients at baseline than in healthy subjects. After treatment, K m normalized in panic patients, whereas V max did not change. A significant inverse correlation was found between increased K m and changes in anxiety levels. These results support a hypothesis of serotonergic transporter abnormalities in panic disorder, and suggest that increased K m values of platelet serotonin transporters parallel clinical improvement after short-term pharmacotherapy in panic disorder.

Evidence-based pharmacotherapy for panic disorder

Evidence-based pharmacotherapy for panic disorder

Genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine in Japanese patients with panic disorder

The objective of this study was to evaluate genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine (PAX) in Japanese patients with panic disorder (PD). Plasma concentration of PAX was determined by high performance liquid chromatography. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) variants were determined by polymerase chain reaction techniques. PD severity was assessed using the Panic and Agoraphobia Scale (PAS). Multiple regression analysis revealed that the plasma concentration of PAX, 5-HTTLPR genotype, and comorbid physical illness were significant factors affecting the initial pharmacotherapeutic effect of PAX in PD and indicated that these factors accounted for 52.4% (R(2) = 0.524) of the variability in the percent reduction in PAS score. The final model was described by the following equation (P = 0.001): percent reduction in PAS score (%) = 68.5 - 1.2 x [plasma concentration of PAX (ng/ml)] - 33.0 x (L/S = 1, S/S = 0) - 21.8 x (with comorbid physical illness = 1, without comorbid physical illness = 0). The high plasma concentration of PAX, the L/S genotype of 5-HTTLPR, and comorbid physical illness might be associated with a poor response to the initial phase of pharmacotherapy of PD with PAX.

Pharmacotherapy of panic disorder

Panic disorder (PD) is a common, persistent and disabling mental disorder. It is often associated with agoraphobia. The present article reviews the current status of pharmacotherapy for PD with or without agoraphobia as well as the current status of treatments combing pharmacotherapy with cognitive behavior therapy (CBT). The review has been written with a focus on randomized controlled trials, meta-analyses, and reviews that have been published over the past few years. Effective pharmacological treatments include tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and various benzodiazepines. Treatment results obtained with CBT compare well with pharmacotherapy, with evidence that CBT is at least as effective as pharmacotherapy. Combining pharmacotherapy with CBT has been found to be superior to antidepressant pharmacotherapy or CBT alone, but only in the acute-phase treatment. Long term studies on treatments combining pharmacotherapy and CBT for PD with or without agoraphobia have found little benefit, however, for combination therapies versus monotherapies. New investigations explore the potential additional value of sequential versus concomitant treatments, of cognitive enhancers and virtual reality exposure therapy, and of education, self management and Internet-based interventions.

Serotonin Function in Panic Disorder: Important, But Why?

The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of intensive interdisciplinary research. Interest in the involvement of 5-HT in PD has been fuelled by clinical studies demonstrating that medications increasing the synaptic availability of 5-HT, such as selective 5-HT re-uptake inhibitors, are effective in the treatment of PD. Rival theories of 5-HT deficiency vs excess have attempted to explain the impact of 5-HT function in PD. In the past decade, knowledge of the role of 5-HT in the neurobiology of PD has expanded dramatically due to much new research including experimental, treatment, brain-imaging, and genetic studies. The current review attempts to summarize the new data and their implications. The challenge and treatment studies generally confirm the specific inhibitory influence of 5-HT on panicogenesis. The brain-imaging studies in PD patients demonstrate functional and clinically relevant alterations in various elements of 5-HT system affecting the neurocircuitry of panic. The findings of genetic association studies suggest that certain 5-HT-related genes may contribute to the susceptibility to PD; however, these data are rather limited and inconsistent. It appears that, even if not the primary etiological factor in PD, the 5-HT function conveys important vulnerability, as well as adaptive factors. A better understanding of these processes may be critical in achieving progress in the treatment of patients suffering from PD.

A meta-analysis of the efficacy of psycho- and pharmacotherapy in panic disorder with and without agoraphobia

The efficacy of (cognitive) behavioural ((C)BT) and pharmacological therapy was investigated using meta-analytic techniques. After a comprehensive review of the literature, the results of 124 studies were included. (C)BT was more effective than a no-treatment control and a placebo control. No difference of efficacy was found when using cognitive elements compared to not using them for anxiety; for associated depressive symptoms, additional cognitive elements seems superior. Pharmacotherapy was more effective than a placebo control; there was no superiority of any drug class. Sample size was related to effect size in pharmacotherapy and publication bias was found. (C)BT was at least as effective as pharmacotherapy and depending on type of analysis even significantly more effective. There were no significant differences between (C)BT alone and a combination approach but characteristics of studies have to be considered.

The pharmacotherapy of panic disorder.

Panic disorder is common and associated with significant morbidity and dysfunction. The pharmacologic treatment of panic disorder is aimed at reducing or eliminating panic attacks, avoidance behavior, anticipatory anxiety, and comorbid conditions--and substantially improving and normalizing overall function and quality of life. Antidepressants and benzodiazepines remain the current mainstays of pharmacotherapy for panic disorder, although other novel agents and strategies are becoming available and may add effective alternatives to the therapeutic armamentarium.

Evidence-based pharmacotherapy of panic disorder

This paper reviews the literature on the pharmacotherapy of panic disorder, in order to address the questions (1) what is the first-line pharmacotherapy of choice for panic disorder?, (2) for how long should maintenance pharmacotherapy be continued, and (3) what is the optimal approach to the treatment-refractory patient with panic disorder. A MEDLINE search (1966-2003) was undertaken to collate randomized controlled trials of pharmacotherapy in panic disorder. A review of the evidence indicates that SSRIs are currently the first line agent of choice in panic disorder, and that pharmacotherapy should be continued for at least 1 year. There has been relatively little research on the pharmacotherapy of treatment-refractory panic disorder, and this area requires future attention.

Pharmacotherapy of panic disorder in the elderly: a naturalistic 12-month follow-up outcome study

Pharmacotherapy of panic disorder in the elderly: a naturalistic 12-month follow-up outcome study

Pharmacotherapy of panic disorder in the elderly: a naturalistic 12-month follow-up outcome study

Background: Despite the previously accepted notion that panic disorder (PD) is rare in the elderly, recent data have shown that late-life PD may be more common than previously thought. Paroxetine is a selective serotonergic reuptake inhibitor which has had clear efficacy in the treatment of PD in the general adult population. In this study we aimed to examine the treatment outcome of paroxetine pharmacotherapy for late-life PD. Method: In this long-term naturalistic follow-up study, a group of 61 elderly (aged 59 years or older) PD patients were compared with a group of 95 younger (aged between 18 and 59 years) PD patients in terms of treatment response to paroxetine pharmacotherapy. The two groups were followed during both the initial short-term treatment phase (first 3 months) and throughout long-term (month 4–12) maintenance treatment. The two groups were also compared for side effects of paroxetine therapy. Results: No differences were found between the two patient groups in terms of response rate, si...

Changes in anxiety sensitivity with pharmacotherapy for panic disorder

Fear of anxiety symptoms (anxiety sensitivity) has been implicated in the etiology and maintenance of panic disorder, and has been shown to improve with cognitive-behavioral treatment. The impact of pharmacotherapy on anxiety sensitivity is less clear. We administered the Anxiety Sensitivity Index (ASI) during a 12-week randomized controlled trial investigating the relative efficacy of paroxetine, paroxetine plus sustained clonazepam, and paroxetine plus brief clonazepam for patients with panic disorder. We found a mean reduction in ASI scores of 9.6 points, which correlated with symptomatic improvement, and did not differ significantly between groups. Our data provides further evidence that pharmacotherapy leads to significant acute reductions in fears of anxiety symptoms in patients with panic disorder, albeit at levels that may be somewhat less than the changes associated with CBT. Implications of these findings are discussed relative to optimizing pharmacologic treatment of panic disorder.

Clomipramine and fluoxetine effects in the treatment of panic disorder

Panic disorder (PD) is an acute psychobiologic reaction manifested by intense anxiety and panic attacks, that occur unpredictably with subjective sense of intense apprehension or terror, accompanied by temporary loss of the ability to plan, think, or reason and the intense desire to escape or flee the situation. Panic attacks may last from a few seconds to an hour or longer. Symptoms typically include, among others, palpitations, tachycardia, hypertension, chest pain, dyspnoea, and fear of loosing control or going crazy and vague feeling of imminent doom or death. Since pharmacotherapy of PD includes the administration of selective serotonin reuptake inhibitors and tricyclic antidepressants, the objective of this study was to perform a pilot double blind clinical trial designed to compare the effects of two studied drugs in the treatment of PD. A total number of 40 patients with a history of panic disorder were randomly assigned into two groups of 20 patients each. Hamilton anxiety rating scale and Standard Psychiatric Interview were methods for PD assessment. One group was treated with clomipramine hydrochloride (ANAFRANIL) 75 mg/day and the other with fluoxetine (OXETIN) 60 mg/day. Both drugs were administrated by mouth (PO) two times-a-day in equally divided doses for 6 weeks. Both studied agents produced similar antipanic effectiveness. Favourable response was achieved in 95% of patients treated with fluoxetine and 90% of patients treated with clomipramine. The onset of antipanic effects was quicker in all clomipramine treated patients, while fluoxetine produced more-favourable response in male patients. The duration of treatment with both antidepressants studied should be at least 10 weeks, instead of 6 weeks.