Pre-treatment peripheral biomarkers associated with treatment response in panic symptoms in patients with major depressive disorder and panic disorder: A 12-week follow-up study

ObjectivePeripheral biomarkers have been studied to predict treatment response of panic symptoms. We hypothesized that depressive disorder (MDD) vs. panic disorder (PD) would exhibit different peripheral biomarkers, and their correlation with severity of panic attacks (PA) would also differ.MethodsForty-one MDD patients, 52 PD patients, and 59 healthy controls were followed for 12 weeks. We measured peripheral biomarkers along with the Panic Disorder Severity Scale (PDSS) at each visit—pre-treatment, 2, 4, 8, and 12 weeks on a regular schedule. Peripheral biomarkers including serum cytokines, plasma and serum brain-derived neurotrophic factor (BDNF), leptin, adiponectin, and C-reactive protein (CRP) were quantified using enzyme-linked immunosorbent assay (ELISA).ResultsPatients with MDD and PD demonstrated significantly higher levels of pre-treatment IL-6 compared to controls, but no differences were seen in plasma and serum BDNF, leptin, adiponectin, and CRP. Pre-treatment leptin showed a significant clinical correlation with reduction of panic symptoms in MDD patients at visit 5 (p = 0.011), whereas pre-treatment IL-6 showed a negative correlation with panic symptom reduction in PD patients (p = 0.022). An improvement in three panic-related items was observed to be positively correlated with pre-treatment leptin in MDD patients: distress during PA, anticipatory anxiety, and occupational interference.ConclusionHigher pre-treatment leptin was associated with better response to treatment regarding panic symptoms in patients with MDD, while higher IL-6 was associated with worse response regarding panic symptoms in PD patients. Different predictive peripheral biomarkers observed in MDD and PD suggest the need for establishing individualized predictive biomarkers, even in cases of similar symptoms observed in different disorders.     

Clinical significance of lifetime panic spectrum symptoms in the treatment of patients with bipolar I disorder

BACKGROUND: Given the observed association between panic disorder and bipolar disorder and the potential negative influence of panic symptoms on the course of bipolar illness, we were interested in the effects of what we have defined as "panic spectrum" conditions on the clinical course and treatment outcome in patients with bipolar I (BPI) disorder. We hypothesized that lifetime panic spectrum features would be associated with higher levels of suicidal ideation and a poorer response to acute treatment of the index mood episode in this patient population. METHODS: A sample of 66 patients with BPI disorder completed a self-report measure of lifetime panic-agoraphobic spectrum symptoms. Patients falling above and below a predefined clinical threshold for panic spectrum were compared for clinical characteristics, the presence of suicidal ideation during acute treatment, and acute treatment response. RESULTS: Half of this outpatient sample reported panic spectrum features above the predefined threshold. These lifetime features were associated with more prior depressive episodes, higher levels of depressive symptoms, and greater suicidal ideation during the acute-treatment phase. Patients with BPI disorder who reported high lifetime panic-agoraphobic spectrum symptom scores took 27 weeks longer than those who reported low scores to remit with acute treatment (44 vs 17 weeks, respectively). CONCLUSIONS: The presence of lifetime panic spectrum symptoms in this sample of patients with BPI disorder was associated with greater levels of depression, more suicidal ideation, and a marked (6-month) delay in time to remission with acute treatment. Alternate treatment strategies are needed for patients with BPI disorder who endorse lifetime panic spectrum features.     

The relationship between positive affect and negative affect during treatment for major depressive disorder

Objective: The present study examined the relationship between positive affect (PA) and negative affect (NA) along the course of combined cognitive behavior therapy and pharmacological treatment for major depressive disorder (MDD). Method: Participants were 165 individuals who sought treatment for MDD in a partial hospital setting. Participants’ PA, NA, and depressive symptoms were measured at pre- and post-treatment and PA and NA were measured at up to 10 additional measurements along the course of treatment. Results: Results indicated that PA at pre-treatment predicted depressive symptoms at post-treatment above and beyond NA and the PA*NA interaction. However, an analysis of patterns of change during treatment using lower level mediational modeling in a multilevel framework indicated that NA predicted subsequent PA to a greater extent than vice versa. Conclusion: Though many treatments for MDD predominantly focus on reducing NA, our findings suggest that PA may be an important predictor of outcome in treatment for MDD, and that the inclusion of interventions to increase the experience of PA may help improve the efficacy of treatment.     

The evaluation of metacognitive beliefs and emotion recognition in panic disorder and generalized anxiety disorder: effects on symptoms and comparison with healthy control

Abstract

Background: The impairments in metacognitive functions and emotion recognition are considered as liable factors in anxiety disorders.

Aims: The better understanding of these cognitive abilities might lead to develop more accurate treatment methods for patients who suffer from anxiety.

Methods: Forty-four patients with panic disorder (PD), 37 individuals with generalized anxiety disorder (GAD) and 44 healthy control (HC) were participated in our study. Metacognition questionnaire-30 (MCQ-30), Reading The Mind From The Eyes Test and symptom severity tests were administered.

Results: Statistical analyses estimated the dysfunctional metacognitive beliefs and disrupted emotion recognition in patients relative to HC. The ‘need to control thoughts’ aspect of metacognitive beliefs was accounted for symptom severity in GAD. Improper metacognitive beliefs were significantly predicted the PD and GAD. In addition, impoverished emotion recognition predicted the GAD.

Conclusions: Our study revealed the role of inconvenient metacognitive beliefs and distorted emotion recognition in PD and GAD. These findings might facilitate the treatment management in cognitive therapies of anxiety disorders via pointing out more reasonable targets across improper cognitive fields.     

Characteristics and course of panic disorder and panic disorder with agoraphobia in primary care patients

Objective: To examine the course of panic disorder (PD) and panic disorder with agoraphobia (PDA) in 235 primary care patients during a 3-year period.Method: Patients were recruited from primary care waiting rooms and diagnosed using the Structured Clinical Interview for DSM-IV. They were reassessed at 6 months, 1 year, and annually thereafter for diagnosis, treatment, and other clinical and demographic variables. Recruitment occurred between July 1997 and May 2001.Results: At intake, 85 patients were diagnosed with PD and 150 were diagnosed with PDA. Patients with PD were significantly more likely to achieve recovery (probability estimate, 0.75) from their disorder than patients with PDA (0.22) at the end of 3-year follow-up (p < .0001). There was no difference in recurrence rates between the 2 disorders. Women were more likely to recover from PD (p = .001). At intake, comorbid generalized anxiety disorder (p = .004), higher Global Assessment of Functioning score (p = .0003), and older age at panic onset (p = .05) were related to recovery from PDA, and comorbid major depressive disorder (p = .05) and psychosocial treatment (p = .002) predicted remaining in an episode of PDA. The relationship between psychosocial treatment and poor recovery must be interpreted with caution and is most likely due to the treatment bias effect.Conclusion: Primary care patients with PDA have a chronic course of illness, whereas those with PD have a more relapsing course. Given the significant burden of PD and PDA in primary care, attention to factors relevant to the course of these disorders is important for recognition and for continued improvement of treatment interventions in this setting.     

Asthma and early smoking associated with high risk of panic disorder in adolescents and young adults

Purpose

Studies have reported a strong link between asthma and panic disorder. We conducted a 17-year community-based large cohort study to examine the relationship between asthma, early smoking initiation, and panic disorder during adolescence and early adulthood.

Methods

A total of 162,766 participants aged 11–16 years were categorized into asthma and nonasthma groups at baseline and compared within the observation period. Covariates during late childhood or adolescence included parental education, cigarette smoking by family members of participants, and participant’s gender, age, alcohol consumption, smoking, and exercise habits. Data for urbanicity, prednisone use, allergic comorbidity, and Charlson comorbidity index were acquired from the National Health Insurance Research Database. The Cox proportional-hazards model was used to evaluate the association between asthma and panic disorder.

Results

Our findings revealed that asthma increased the risk of panic disorder after adjustment for key confounders in the Cox proportional hazard regression model (adjusted HR: 1.70, 95% CI 1.28–2.26). Hospitalizations or visits to the emergency department for asthma exhibited a dose–response effect on the panic disorder (adjusted HR: 2.07, 95% CI 1.30–3.29). Patients with asthma with onset before 20 years of age who smoked during late childhood or adolescence had the greatest risk for panic disorder (adjusted HR: 4.95, 95% CI 1.23–19.90).

Conclusions

Patients newly diagnosed with asthma had a 1.7-times higher risk of developing panic disorder. Smoking during late childhood or adolescence increased the risk for developing the panic disorder in patients with asthma.

     

Emergence of depressive symptoms during treatment for panic disorder with specific 5-hydroxytryptophan reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRI) have been established as effective drugs in the treatment of depressive and anxiety disorders. However, there are also reports that they can induce depressive symptoms and suicidal thoughts in patients. Eighty of 230 patients who met the DSM-III-R criteria for panic disorder received, during the course of treatment, fluvoxamine (a selective serotonin reuptake inhibitor) at a dose level between 50–200 mg/day. The patients were clinically evaluated for a history of affective disorder and for the presence of affective symptoms before the treatment and for emergence of depressive symptoms during the treatment. Seven of the 80 patients (9%) developed symptoms of depression despite a good antianxiety response. Five of the 7 patients received fluvoxamine as second choice after tricyclic antidepressants (TCA). These patients had no history of affective disorder, and no symptoms of depression were present before the treatment with fluvoxamine. The depressive symptoms abated after the fluvoxamine was discontinued and TCA or clonazepam was prescribed. The depressive symptoms reappeared when fluoxetine was administered. None of these 7 patients developed depressive symptoms while treated with TCA or clonazepam. Among the 150 patients treated with TCA and benzodiazepines, not a single case of depression was seen in patients without a previous history of depression. These results suggest a vulnerability among some of panic disorder patients to noradrenergic-serotonergic imbalance caused by SSRI, which has to be taken into clinical consideration.     

Childhood trauma and dissociative symptoms in panic disorder

OBJECTIVE: Childhood trauma has been associated with increased risk for both panic disorder and dissociative symptoms in adulthood. The authors hypothesized that among individuals with a primary diagnosis of panic disorder, those experiencing depersonalization/derealization during panic attacks would be more likely to have a history of childhood trauma. METHOD: Rates of traumatic events were compared between panic disorder patients with (N=34) and without (N=40) prominent depersonalization/derealization during panic attacks. Symptom severity in the two groups was also examined. RESULTS: Contrary to the authors' hypothesis, no evidence was found that depersonalization/derealization during panic attacks was associated with childhood trauma. Minimal differences in severity of illness were found between patients with dissociative symptoms and those without such symptoms. CONCLUSIONS: This finding is consistent with a multifactorial model of dissociation. Factors other than childhood trauma and general psychopathology may underlie vulnerability to dissociative symptoms in panic disorder.     

Comorbid panic disorder as an independent risk factor for suicide attempts in depressed outpatients

ObjectiveAlthough comorbid panic disorder is associated with more severe symptoms and poorer therapeutic response in depressive patients, the relationship between panic disorder and risk of suicide attempt has not been confirmed. This study aimed to examine the relationship between comorbid panic disorder and clinical characteristics associated with suicidal risk as well as the likelihood of suicide attempt.MethodA total of 223 outpatients with current major depressive disorder participated in the study. Both subjects with panic disorder (33%) and those without panic disorder (67%) were compared based on history of suicide attempts, current psychopathologies, and traits of impulsivity and anger.ResultsSubjects with panic disorder had higher levels of impulsivity, depression, and hopelessness and were more likely to report a history of suicide attempts. Subjects with panic disorder were younger at the time of first suicide attempt than those without panic disorder. Logistic regression analyses indicated that comorbid panic disorder was significantly associated with a history of suicide attempts after adjusting for other clinical correlates (odds ratio = 2.8; p < 0.01).ConclusionsThese findings suggest that comorbid panic disorder in patients with major depressive disorder may be associated with a more severe burden of illness and may independently increase the likelihood of suicide attempt.     

Temperament and character dimensions and their relationship to major depression and panic disorder

IntroductionSince the first publication of Cloninger's psychobiological model of personality, the relationship between temperament and character dimensions and psychiatric disorders has been widely studied. The exact nature of this interaction, however, is still unclear. Different models have been proposed (state-dependency, vulnerability, continuous spectrum etc).ObjectiveTo analyze the relationship between temperament and character dimensions with depression and panic disorder.MethodSystematic review on interventional studies published up until December 2011 on MEDLINE and ISI databases. Also, a brief review on genetic studies is hereby undertaken, aiming to discuss the gene-environment interaction in relation to this topic.Results:Thirteen studies were included: 10 related to depression and 3 to panic disorder (or unspecific anxiety symptoms). All of them showed association between high harm avoidance (HA) and low self-directedness (SD) with depression and anxiety symptoms. Longitudinal studies demonstrated that these traits may not be just state-dependent.Conclusions:HA and SD dimensions are associated with both the occurrence of depressive and anxiety symptoms. There is also some evidence to suggest that high HA and low SD indicates susceptibility to depression. Longitudinal studies are not sufficient to affirm the same about panic disorder up to the present moment.     

Mirtazapine versus paroxetine in panic disorder: an open study

Introduction

Open studies suggest that mirtazapine has efficacy in panic disorder treatment. We designed an open study that evaluates changes induced by mirtazapine compared with paroxetine in panic disorder.

Methodology

Patients 18–65 years old consecutively referred to a psychiatry liaison service with panic disorder (DSM-IV criteria) were offered either mirtazapine or paroxetine treatment.

Results

There were statistically significant reductions from baseline to week 3 and from week 3 to 8 for mirtazapine and paroxetine groups for: number of panic attacks, Beck Anxiety or Depression Inventory (BAI, BDI) Clinical Global Impresion (CGI) of panic disorder severity and CGI of panic disorder response (these variables were evaluated by the patient, the clinician or a blind evaluator). Responders at week 3 (BAI decrease of 50%) were 83% for the mirtazapine group and 84% for the paroxetine group. Responders at week 8 (number of panic attacks equal to 0) were 77% for the mirtazapine group and 73% for the paroxetine group Statistically significant differences between mirtazapine and paroxetine were found for number of panic attacks at weeks 3 and 8 and BAI at week 3, suggesting a faster response for mirtazapine. Responders at week 8 maintained a no recurrence figure of 95% at follow-up 6 months later. Panic disorder either with or without comorbid depression improved in both groups of treatment.

Discussion

Our study supports the hypothesis that mirtazapine has efficacy in the treatment of panic disorder either with or without comorbid depression.     

Hypofrontality in panic disorder and major depressive disorder assessed by multi-channel near-infrared spectroscopy

Background: Panic disorder is a common and debilitating psychiatric disease; yet, the neurobiology of this disorder is not fully understood. Deficits in the prefrontal inhibitory control over hyperactivity of the anxiety‐related neural circuit are implicated in the pathophysiological core of panic disorder. The aims of this study were to investigate whether panic disorder reveals frontal lobe dysfunction while performing the word fluency test by using multi‐channel near‐infrared spectroscopy and to compare the findings in panic disorder with those in major depressive disorder. Methods: Twenty‐one patients with panic disorder, 17 patients with major depressive disorder, and 24 healthy control subjects participated in the study. Results: Both patients with panic disorder and with major depressive disorder showed similarly attenuated increases in oxy‐hemoglobin during the word fluency test in the bilateral frontal regions, when compared to healthy control participants. Hypofrontality in panic disorder and major depressive disorder was most prominent in the left medial inferior frontal lobe. Conclusions: This study clarified that hypofrontality in panic disorder is evident even with neutral stimuli of little emotional load. Depression and Anxiety 25, 2008. © 2008 Wiley‐Liss, Inc.     

Hypochondriacal concerns in panic disorder and major depressive disorder: a comparison

OBJECTIVE: To gain perspective on the relationship between hypochondriasis and panic disorder, we compared the occurrence of hypochondriasis in patients with panic disorder (N= 59) and major depressive disorder (N= 27). METHODS: Patients who participated in separate drug treatment trials were assessed at baseline and eight weeks using the Whiteley Index of Hypochondriasis. RESULTS: At baseline, the Whiteley Index score was greater for patients with panic disorder than for those with major depressive disorder. At eight weeks, a statistically significant reduction in the mean hypochondriasis score was observed in panic patients who had improved but not in major depressive patients who had improved. Modest correlations were observed between hypochondriasis and symptoms of panic and major depressive disorder, but in depressed patients, hypochondriasis was positively correlated with anxiety symptoms as well. CONCLUSION: A unique relationship appears to exist between hypochondriasis and panic disorder. The nature of this relationship and its implications for classification are discussed.     

Psychoticism in patients with panic disorder with or without comorbid agoraphobia

Objective: A few case-reports have previously described transient psychotic-like symptoms in non-psychotic patients with panic disorder (PD). We aimed to systematically explore whether PD patients without any current or past psychosis can be differentiated according to the severity of ‘psychoticism’ as a dimension, comprising clinical features such as psychotic-like experiences, increased social alienation, hostility and suspiciousness.

Methods: Sample included 35 (female?=?26) medication-free, non-psychotic patients consecutively referred from our Department’s Outpatient Clinic for acute symptoms of DSM-5 PD with (PDA; N?=?29) or without concurrent agoraphobia. Psychometric measures included the Symptom Checklist–90–Revised (SCL-90-R), Agoraphobic Cognitions Questionnaire (ACQ), Body Sensations Questionnaire (BSQ), and panic attacks during last 21 days PA-21d.

Results: Multiple regression analysis (forward stepwise) revealed that, among all SCL-90-R subscales, the psychoticism-subscale was most significantly associated with panic-related beliefs included in the ACQ, while significant associations emerged between the paranoid ideation-subscale and the ACQ and BSQ measures. Moreover, significant correlations emerged between the SCL-90-R psychoticism-subscale and all three measures of PD symptoms (ACQ, BSQ, PA-21d) and between the SCL-90-R paranoid ideation-subscale and both the ACQ and BSQ.

Conclusions: This significant association between levels of psychoticism and severity of panic symptoms may reflect a more severe subtype of PD.     

Experimental affective symptoms in panic disorder patients.

OBJECTIVE: To date, carbon dioxide (CO2) challenge tests in panic disorder (PD) patients have focused on anxiety as the sole outcome measure. This study assesses a broader range of symptoms in patients with PD. METHOD: We administered a gas mixture of 35% CO2 and 65% oxygen (O2) to 25 patients with PD. Nine patients met the criteria for a comorbid major depressive disorder (MDD), and 16 did not. We assessed not only subjects' symptoms of anxiety but also their symptoms of depression and aggression. RESULTS: Baseline ratings did not differ across the 2 subgroups. Postchallenge ratings were higher for PD and MDD patients on all the assessed affective symptoms, except for specific panic symptoms. CONCLUSION: These findings suggest that, in addition to anxiety, CO2 challenge induces depressive and aggressive symptoms, specifically in PD patients with comorbid depression.     

Improvement in adult anxious and avoidant attachment during cognitive behavioral therapy for panic disorder

Objective: This study examined attachment within the framework of cognitive behavioral therapy (CBT) for panic disorder with agoraphobia (PDA) by measuring the changes in avoidant and anxious attachment in a session-by-session analysis. Method: Thirty-one patients with PDA were treated using CBT. Pre-session data on attachment style (ECR), avoidance behaviors (MI-alone: MI-al; MI-accompanied: MI-ac), anxiety sensitivity (ASI), emotion regulation (ERQ), and working alliance (WAI) were collected. Mixed model analyses were conducted to estimate relationship between changes in attachment, PDA symptoms, and related measures. Results: Variables improved during therapy. Changes in ASI were positively related to changes in avoidant and anxious attachment. Changes in MI-al, but not MI-ac, were related to changes in ECR. Changes in ASI and MI-al predicted changes in ECR-anxiety in the following session, but not vice versa. Similarly, changes in avoidance behaviors and ERQ-suppression, preceded changes in ECR-avoidance unidirectionally. Whereas WAI significantly improved, its variability was related only to simultaneous changes in ECR-anxiety. Conclusions: Overall, avoidant and anxious attachment improved during CBT for PDA. This change was related to and preceded by improved anxiety sensitivity, avoidance behaviors, and emotion regulation. These findings suggest that CBT for panic probably has downstream effects on attachment representations.

Clinical or methodological significance of this article: This is the first report of changes in attachment via cognitive behavioral therapy for panic disorder. Data were examined using repeated measures session by session, allowing for examination of temporal precedence of changes. Results revealed that anxiety sensitivity, avoidance, and suppression preceded changes in attachment. Results are discussed in the framework of modern attachment theory models.     

Obsessive-compulsive symptoms in panic disorder

Previous reports have noted an increased prevalence of obsessive-compulsive symptoms in patients with panic disorder. The authors found a prevalence of obsessive-compulsive symptoms in 19 (27%) of 70 patients with panic disorder. Compared to a subgroup of 25 patients with classic features of panic disorder and no obsessive-compulsive symptoms, the subgroup with obsessive-compulsive symptoms had an earlier onset of illness, were more likely to have personal and family histories of major depression and substance abuse, and showed a poorer outcome after treatment.     

Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder

OBJECTIVE: To evaluate the efficacy and tolerability of sertraline and imipramine in patients with comorbid panic disorder and major depressive disorder. METHOD: Outpatients meeting a DSM-IV diagnosis of panic disorder and concurrent major depressive disorder were randomized in a 2:1 ratio to 26 weeks of double-blind treatment with either sertraline, in daily doses of 50 to 100 mg, or imipramine, in daily doses of 100 to 200 mg. Primary outcome measures were panic attack frequency (derived from patient diaries) and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: 138 patients were treated with sertraline (76% female; mean age = 40 years) and 69 with imipramine (70% female; mean age = 40 years). The symptoms of both major depressive disorder and panic disorder responded significantly and equivalently to both drugs. Endpoint improvement with sertraline versus imipramine, respectively, on the MADRS was 11.1 +/- 10.8 versus 11.2 +/- 10.4, and on the Clinical Global Impressions-Improvement scale (CGI-I) was 2.1 +/- 1.3 versus 2.4 +/- 1.6. Among study completers, CGI-I responder rates were 88% with sertraline and 91% with imipramine. Treatment outcome was concordant for both diagnoses in approximately 70% of patients and discordant in approximately 30%. Overall, sertraline was significantly better tolerated with significantly fewer discontinuations due to adverse events (11% vs. 22%; chi(2) = 4.39, df = 1, p =.04). CONCLUSION: Both sertraline and imipramine were found to be highly effective treatments for both major depressive disorder and panic disorder, with sertraline showing significantly greater tolerability and compliance during long-term treatment than imipramine.     

Treatment of mitral valve prolapse and panic disorder with metoprolol

Summary: The prevalence of mitral valve prolapse (MVP) and panic disorder (PD) has been reported to range from 0-50% depending on the respective diagnostic manuals and described selection criteria. We report the case of a 44-year-old patient suffering from both panic disorder and mitral valve prolapse. While antidepressants did not result in any improvement of panic symptoms, a fast remission was achieved by treating the patient with metoprolol. This case report suggests that betablockers might represent a useful tool in the treatment of panic disorder and mitral valve prolapse.     

Citalopram controls phobic symptoms in patients with panic disorder: randomized controlled trial

OBJECTIVE: To examine the effects of long-term treatment with citalopram or clomipramine on subjective phobic symptoms in patients with panic disorder. DESIGN: Double-blind, parallel-group, five-arm study. PATIENTS: Patients aged 18 to 65 years with panic disorder (DMS-III-R diagnosis) and with no major depressive symptoms. INTERVENTIONS: Four hundred and seventy-five patients were randomized to 8 weeks of treatment with either citalopram (10 to 15 mg per day; 20 to 30 mg per day; or 40 to 60 mg per day), clomipramine (60 to 90 mg per day) or placebo. Two hundred and seventy-nine patients continued treatment after the 8-week acute phase. OUTCOME MEASURES: Phobic symptoms were assessed using the Phobia Scale and the Symptom Checklist's (SCL-90) phobia-related factors. RESULTS: At all dosages, citalopram was more efficacious than placebo, with 20 to 30 mg generally being the most effective dosage. Citalopram (20 to 30 mg) generally decreased phobic symptoms significantly more than placebo after Month 3. Interpersonal sensitivity decreased when measured on the respective SCL-90 sub-scale. Alleviation of phobic symptoms generally continued to increase towards the end of the treatment. The effect of clomipramine was not as consistent. CONCLUSIONS: All active treatment groups, especially the group receiving 20 to 30 mg per day of citalopram, effectively controlled phobic symptoms in patients with panic disorder. Long-term treatment with citalopram further decreased phobic symptoms.