Quetiapine extended-release augmentation has not been found to be beneficial , in comparison to placebo , in non-responders to previously recommended pharmacotherapy .
In non-responders to cognitive behavioral therapy ( CBT ) , switching to paroxetine/citalopram has been found to be more effective than continuing CBT .
Acceptance and commitment therapy ( ACT ) has shown some improvement in patients ’ resistance to previous psychological/pharmacological interventions compared with a waiting-list condition .
Prolonged pharmacotherapy may produce significant improvement in patients with unsatisfactory response to short-term pharmacotherapy  , while switching to pharmacotherapy may help non-responders to CBT .
Purpose of Review Purpose of Review Management of treatment-resistant ( TR ) panic disorder ( PD ) is an unresolved issue .
In this paper , we provide a brief summary of previous findings , an up date d ( 2015–2017 ) systematic review of pharmacological/non-pharmacological studies , and our personal perspective on this topic .
Next-step strategies for panic disorder refractory to initial pharmacotherapy: a 3-phase randomized clinical trial.
BACKGROUND More data are needed to guide next-step interventions for panic disorder refractory to initial intervention . METHOD This 24-week r and omized clinical trial ( RCT ) enrolled 46 patients with DSM-IV-defined panic disorder from November 2000 to April 2005 and consisted of 3 phases . Patients who failed to meet remission criteria were eligible for r and omization in the next treatment phase . Phase 1 was a 6-week lead-in with open-label sertraline flexibly dosed to 100 mg ( or escitalopram equivalent ) to prospect ively define treatment refractoriness ( lack of remission ) . Phase 2 was a 6-week double-blind RCT of ( 1 ) increased-dose selective serotonin reuptake inhibitor ( SSRI ) versus ( 2 ) continued SSRI plus placebo . Phase 3 was a 12-week RCT of added cognitive-behavioral therapy ( CBT ) compared to " medication optimization " with SSRI plus clonazepam . Primary endpoints were remission and change in Panic Disorder Severity Scale ( PDSS ) score in the intent-to-treat sample in each phase . RESULTS In phase 1 , 20.5 % ( 8/39 ) of the patients achieved remission , and only baseline severity predicted endpoint PDSS score ( beta [ SE ] = 1.04 [ 0.15 ] , t = 6.76 , P < .001 ) . In phase 2 , increasing the SSRI dose did not result in greater improvement or remission rates  ( placebo 15 % [ n = 2 ] vs increased dose 9 % [ n = 1 ] : Fisher exact test P = NS ) . In phase 3 , remission was minimal ( medication optimization = 11 % [ n = 1 ] ; CBT = 10 % [ n = 1 ] ) , with a lack of group difference in PDSS score reduction ( t(17 ) = 0.51 , P > .60 ) consistent with a small effect size ( d = 0.24 ) . CONCLUSIONS Although power was limited and larger studies are needed , we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose . Further , augmentation with CBT or medication optimization with clonazepam augmentation in nonremitted panic after 12 weeks of an SSRI did not differ , suggesting that both are reasonable next-step options . However , low overall remission rates in this comorbid refractory population suggest that better predictors of response to specific treatments over time and additional interventions are needed . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00118417
Quetiapine extended-release augmentation has not been found to be beneficial , in comparison to placebo , in non-responders to previously recommended pharmacotherapy .
In non-responders to cognitive behavioral therapy ( CBT ) , switching to paroxetine/citalopram has been found to be more effective than continuing CBT .
Acceptance and commitment therapy ( ACT ) has shown some improvement in patients ’ resistance to previous psychological/pharmacological interventions compared with a waiting-list condition .
Prolonged pharmacotherapy may produce significant improvement in patients with unsatisfactory response to short-term pharmacotherapy  , while switching to pharmacotherapy may help non-responders to CBT .
Purpose of Review Purpose of Review Management of treatment-resistant ( TR ) panic disorder ( PD ) is an unresolved issue .
In this paper , we provide a brief summary of previous findings , an up date d ( 2015–2017 ) systematic review of pharmacological/non-pharmacological studies , and our personal perspective on this topic .