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.     

Sertraline treatment of panic disorder: results of a long-term study.

OBJECTIVE: To investigate the long-term efficacy, prevention of relapse and safety of sertraline in the treatment of panic disorder. METHOD: This study consisted of 52 weeks of open-label sertraline treatment (n=398) followed by a 28 weeks of a double-blind, placebo-controlled discontinuation trial (n=183). RESULTS: Ninety-three patients were randomized to sertraline and 90 were randomized to placebo. Discontinuation due to insufficient clinical response occurred in 23.6% of placebo-treated patients and 12.0% of sertraline-treated patients (log-rank test, P=0.040). Thirty-three per cent of placebo-treated patients had an exacerbation of panic symptomatology, versus 13% of sertraline-treated patients (log-rank test, P=0.005). Abrupt cessation of sertraline resulted in dizziness (4.3% sertraline vs. 16.9% placebo; P=0.007) and insomnia (4.3% sertraline vs. 15.7% placebo; P=0.013) occurring at significantly higher rates. CONCLUSION: Long-term sertraline treatment was effective in preventing relapse of panic disorder, well tolerated and associated with minimal discontinuation symptoms.     

Unemployment and emergency room visits predict poor treatment outcome in primary care panic disorder

BACKGROUND: To complement existing data on predictors of treatment response in groups of "pure" panic disorder patients studied in clinical trials or in poorly controlled naturalistic follow-up, we sought to elucidate predictors of treatment response over 1 year in a diagnostically heterogeneous and comorbidly ill group of primary care patients with panic disorder participating in a randomized effectiveness study. METHOD: Patients with DSM-IV panic disorder (N = 115), mostly without agoraphobia, were recruited from 3 primary care clinics in Seattle, Wash., and randomly assigned to an on-site collaborative care intervention (N = 57), in which psychiatrists provided education, 2 visits, follow-up phone calls, and paroxetine, or to usual care by their primary care physician (N = 58). Predictors of response at 3-month intervals over 1 year were determined using logistic regression analysis. RESULTS: Patients with consistent response over the year (response at the majority of available timepoints) were significantly (p <.05) more likely to be white, employed, in higher income strata, and in the intervention group and had less medical comorbidity and phobia severity, fewer recent hospitalizations and emergency room visits, and higher reported Medical Outcomes Study 36-Item Short Form physical and role functioning. The final regression model indicated that responders were more likely to be in the intervention group, be employed, and lack a recent emergency room visit. CONCLUSION: While some of the univariate findings partially replicate previous results linking greater illness severity with poorer response, univariate findings linking medical comorbidity and low socioeconomic status with poor response, as well as multivariate findings that unemployment and recent emergency room use are the most potent predictors of poor response, have not been previously reported.     

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.     

Face-emotion processing in offspring at risk for panic disorder

OBJECTIVE: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. METHOD: Offspring of adults with PD, major depressive disorder (MDD), or no disorder (ages 9-19) viewed computer-presented face photographs depicting angry, fearful, and happy faces. Offspring rated (1) subjectively experienced fear level, (2) how hostile the face appeared, and (3) nose width. Attention allocation was indexed by latency to perform ratings. RESULTS: Compared with offspring of parents without PD (n = 79), offspring of PD parents (n = 65) reported significantly more fear and had slower reaction times to rate fear, controlling for ongoing anxiety disorder in the offspring. Offspring with an anxiety disorder (n = 65) reported significantly more fear than offspring without an anxiety disorder but not when parental PD was controlled. Social phobia but no other anxiety disorder in offspring was associated with slower reaction times for fear ratings (but not greater fear ratings). Parental PD and offspring social phobia independently predicted slower reaction time. CONCLUSIONS: Results support an association between parental PD and offspring responses to fear provocation. Social phobia in children may have a specific relationship to allocation of attention to subjective anxiety during face viewing.     

Early age at onset as a risk factor for poor outcome of bipolar disorder

The primary aim of our study was to investigate the effect of the age at onset (AAO) of Bipolar Disorder (BP) on the clinical course of the illness. We studied 320 subjects with a diagnosis of BP I or BP II who had been previously recruited for a genetic research protocol. All subjects gave their informed consent to participate in the study. Each subject was interviewed using the SCID I. The main clinical variables were compared between subjects with early (/=18 years) age at onset of BP (chi square tests and t-tests for independent samples). In addition, a logistic regression analysis was applied to the variables that were significantly related to earlier onset of BP in the exploratory analyses. We found a significantly earlier AAO in subjects with anxiety disorders (t=2.44, P=0.015) and rapid cycling course (t=3.16, P=0.002). When we compared a number of clinical characteristics between early and later onset of BP, subjects with early AAO had more frequent suicidal ideation/attempts (chi(2)=12.12, P=0.002), Axis I comorbidity (chi(2)=8.12, P=0.004), substance use disorders (chi(2)=5.45, P=0.019) and rapid cycling course (chi(2)=9.87, P=0.002). The Odds Ratios associated with these variables were: 1.407 (suicide ideation), 1.646 (Axis I comorbidity), 1.468 (substance abuse), and 2.082 (rapid cycling course). Overall, these results suggest a role of early AAO as a significant predictor of poor outcome in BP and, if replicated, they may have important clinical implications.     

Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison

OBJECTIVE: Several classes of medications have demonstrated efficacy in panic disorder, but direct comparison of 2 proven treatments is still uncommon. The purpose of this study was to compare sertraline and paroxetine in the acute treatment of panic disorder. METHOD: Adult outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10 criteria) were randomly assigned in double-blind fashion to 12 weeks of treatment with flexible doses of sertraline (titrated up to 50-150 mg/day; N = 112) or paroxetine (titrated up to 40-60 mg/day; N = 113). Patients were then tapered off medication over 3 weeks. The primary analysis was a noninferiority analysis of Panic and Agoraphobia Scale (PAS) scores. Secondary measures included panic attack frequency and the Clinical Global Impressions-Improvement scale (CGI-I) (with responders defined as those with a CGI-I score < or = 2). Data were collected from January 2000 to June 2001. RESULTS: Sertraline and paroxetine were associated with equivalent levels of improvement on the PAS total score, as well as on all secondary outcome measures. Eighty-two percent of patients taking sertraline versus 78% of those taking paroxetine were CGI-I responders at endpoint. Numerically more patients on paroxetine treatment compared with sertraline treatment discontinued due to adverse events (18% vs. 12%; NS), and a significantly higher proportion of paroxetine patients showed > or = 7% weight gain (7% vs. < 1%; p <.05). During the taper period, the proportion of panic-free patients increased by 4% with sertraline but decreased by 11% with paroxetine (p <.05). CONCLUSION: Sertraline and paroxetine had equivalent efficacy in panic disorder, but sertraline was significantly better tolerated and was associated with significantly less clinical worsening during taper than paroxetine.     

HPA axis disturbance and treatment outcome in panic disorder

Some patients with panic disorder exhibit an abnormal response to dexamethasone. As this phenomenon may reflect disturbances in the central noradrenergic system and as alprazolam may work through this system to produce improvement, we predicted a particularly robust response among nonsuppressors. Fifty-two patients with panic disorder or with agoraphobia with panic attacks were given alprazolam as the sole treatment during either of 2, 8-week, double-blind, placebo-controlled trials. Though baseline clinical severity predicted globally rated outcome, baseline Dexamethasone Suppression Test results did not.     

Poverty and response to treatment among panic disorder patients in primary care

OBJECTIVE: Despite well-established links between poverty and poor mental illness outcome as well as recent reports exploring racial and ethnic health disparities, little is known about the outcomes of evidence-based psychiatric treatment for poor individuals. METHOD: Primary care patients with panic disorder (N=232) who were participating in a randomized controlled trial comparing a cognitive behavior therapy (CBT) and pharmacotherapy intervention to usual care were divided into those patients above (N=152) and below (N=80) the poverty line. Telephone assessments at 3, 6, 9, and 12 months were used to compare the amount of evidence-based care received as well as clinical and functional outcomes. RESULTS: Poor subjects were more severely ill at baseline, with more medical and psychiatric comorbidity. The increases in the amount of evidence-based care and reductions in clinical symptoms and disability were comparable in the two groups such that poorer individuals, although responding equivalently, continued to be more ill and disabled at 12 months. CONCLUSIONS: The comparable response of poor individuals in this study suggests that standard CBT and pharmacotherapy treatments for panic disorder do not need to be "tailored" to be effective in poor populations. However, the more severe illness both at baseline and follow-up in these poor individuals suggests that treatment programs may need to be extended in order to treat residual symptoms and disability in these patients so that they might achieve comparable levels of remission.     

The effect of pharmacotherapist characteristics on treatment outcome in panic disorder

A large number of studies suggest that individual characteristics of psychotherapists affect the outcome of psychosocial treatments for psychiatric illness, but little work has been done to see if this is also the case for pharmacotherapy. In the context of a multicenter study that compared psychosocial and medication treatments for panic disorder, we assessed whether such characteristics as age of the psychiatrist, number of years of experience, and gender influence the outcome of treatment with the antipanic drug imipramine. Data were examined by multiple and logistic regression analyses for eight psychiatrists who treated a total of 57 patients with panic disorder. More physician experience, measured as years since completing residency, was associated with better response to imipramine on one of two main dichotomous measures (the Clinical Global Impression-Improvement Scale) and on six of nine continuous measure rating scales. Associations between psychiatrist age and outcome and between psychiatrist gender and outcome were also present but on fewer measures. Although these are post-hoc analyses that were not planned when the multicenter study was originally designed and therefore there are limitations in the information available about the psychiatrists' characteristics, the findings suggest that even in the context of a clinical trial that employs a specific protocol and single medication, physician experience may influence patient outcome. Depression and Anxiety 17:88-93, 2003.     

Placebo response in panic disorder

Of 43 patients with panic disorder or agoraphobia with panic attacks who took placebo for 8 weeks in two double-blind studies, one in four markedly improved. Those with consistently normal dexamethasone suppression test results were significantly more likely to show a placebo response as were those with lower anxiety ratings at the outset of treatment.     

Growth hormone response to clonidine in panic disorder patients

The growth hormone (GH) response to clonidine administration (2 micrograms/kg) was compared in three groups of subjects: seven panic disorder patients, seven depressed patients matched for age and sex, and seven normal controls. As previously reported, patients with affective disorders show a blunted GH response to clonidine. Only one panic disorder patient had a blunted GH response to clonidine, and this patient had recently received a tricyclic antidepressant.     

Prolactin response to TRH in patients with panic disorder

The effects of TRH administration (400 microg, i.v.) on the release of prolactin were examined in 15 patients who met DSM-III-R criteria for panic disorder and 15 normal control subjects. Four hundred micrograms TRH was given via IV route. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. The results demonstrate that prolactin responses to TRH did not differ between panic disorder patients and normal control subjects. When only women were evaluated, the findings indicate that women with PD tend to show excessive prolactin responses to TRH. The findings are discussed in view of findings from earlier reports.     

Patterns of response during placebo treatment of panic disorder

Data from the cross-national study of panic disorder are used for an analysis of response patterns. The main purpose of the study is a search for specific placebo patterns and a discussion of possible differences in patterns from patients treated with alprazolam, imipramine, and placebo. Four outcome measures were registered at baseline and weekly during the treatment period: the number of panic attacks, Physician's Global Evaluation of treatment effect, the Overall Phobia Score and the level on the Hamilton Rating Scale for Anxiety. Response patterns from the 3 treatment groups are described and compared, and subsequently categorized with regard to completeness and persistency. No specific placebo pattern is recognized. Some differences are found, however, as many placebo patients demonstrate an early and temporary remission. The variations in response patterns do not compromise the blindness of the study, and their predictive validity is low.     

Alexithymia and anxiety sensitivity in populations at high risk for panic disorder

ObjectivePopulations at high risk for panic disorder (PD) probably share with subjects with PD an underlying vulnerability involving features like anxiety sensitivity (AS) and alexithymia. The present study would verify if PD relatives (R) and subjects who have experienced 1 or more panic attacks (PAs) show different levels of AS and alexithymia with respect to healthy controls (HC).MethodsOne hundred fifty-seven HCs, 30 subjects with PA, 64 R subjects, and 139 outpatients with PD were evaluated and compared on AS, alexithymia, and control variables.ResultsSubjects with PD show higher alexithymia and AS levels compared with HCs; R subjects do not differ on ASI total score; and R females show more alexithymic features. Subjects with PA are comparable with HCs both on AS and alexithymia.ConclusionsResults confirm an impairment in emotional and bodily sensations information processing in subjects with PD but partially disconfirm the expectation of a difference between R subjects and subjects with PA with respect to HCs on AS and alexithymia. Emotional and bodily sensation competencies could be protective factors for PD in high-risk populations.     

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.     

Controlled discontinuation of benzodiazepine treatment for patients with panic disorder

OBJECTIVE: The purpose of this study was to compare the effects of discontinuing treatment with intermediate- and long-acting benzodiazepines. METHOD: Fifty patients with panic disorder who had taken part in a double-blind treatment study and had responded to alprazolam, diazepam, or placebo for 8 months were asked to stop taking these medications gradually. RESULTS: After a relatively rapid dose reduction, the majority of patients relapsed. Rebound anxiety and withdrawal symptoms were identified in a substantial minority of patients. Those who were taking alprazolam showed earlier and more intense rebound anxiety and withdrawal symptoms than did the patients who received diazepam. Both the level of pretreatment anxiety and the drug the patient was taking predicted the level of anxiety when drug treatment was discontinued. CONCLUSIONS: The findings indicate that withdrawal phenomena commonly occur after patients stop taking benzodiazepines and that they are more frequent after discontinuation of treatment with shorter-acting drugs.     

Cognitive-behavioral treatment for panic disorder: current status

Is cognitive behavioral treatment (CBT) appropriate for panic disorder with or without agoraphobia (PDA) in children, adolescents, and adults? Are its effects durable? In this review, we survey various psychological approaches to the treatment of PDA and examine the relative efficacy and clinical utility of each. A growing body of research demonstrates that CBT is well-tolerated, cost-effective, and produces substantial treatment gains for individuals with PDA over the short- and long-term. Nevertheless, not everyone benefits and there is room for improvement among those who do. We address these shortcomings and consider recent developments.