Combination of Psychotherapy and Benzodiazepines versus Either Therapy
Combination of Psychotherapy and Benzodiazepines versus Either Therapy
Background: The efficacy of combined psychotherapy and benzodiazepine treatment for panic disorder is still unclear despite its widespread use. The present systematic review aims to examine its efficacy compared with either monotherapy alone.
Methods: All randomised trials comparing combined psychotherapy and benzodiazepine for panic disorder with either therapy alone were identified by comprehensive electronic search on the Cochrane Registers, by checking references of relevant studies and of other reviews, and by contacting experts in the field. Two reviewers independently checked eligibility of trials, assessed quality of trials and extracted data from eligible trials using a standardized data extraction form. Our primary outcome was "response" defined by global judgement. Authors of the original trials were contacted for further unpublished data. Meta-analyses were undertaken synthesizing data from all relevant trials.
Results: Only two studies, which compared the combination with behaviour (exposure) therapy, met our eligibility criteria. Both studies had a 16-week intervention. Unpublished data were retrieved for one study. The relative risk for response for the combination was 1.25 (95%CI: 0.78 to 2.03) during acute phase treatment, 0.78 (0.45 to 1.35) at the end of treatment, and 0.62 (0.36 to 1.07) at 6-12 months follow-up. Some secondary outcomes hinted at superiority of the combination during acute phase treatment.
One study was identified comparing the combination to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98), 3.39 (1.03 to 11.21, statistically significant) and 2.31 (0.79 to 6.74) respectively. The superiority of the combination was observed on secondary outcomes at all the time points. No sub-group analyses were conducted due to the limited number of included trials.
Conclusion: Unlike some narrative reviews in the literature, our systematic search established the paucity of high quality evidence for or against the combined psychotherapy plus benzodiazepine therapy for panic disorder. Based on limited available published and unpublished data, however, the combined therapy is probably to be recommended over benzodiazepine alone for panic disorder with agoraphobia. The combination might be superior to behaviour therapy alone during the acute phase, but afterwards this trend may be reversed. We know little from these trials about their adverse effects.
Panic disorder is characterized by the repeated occurrence of unexpected panic attacks, i.e. abrupt strong fears with anticipation of death, often accompanied by somatic symptoms such as palpitations, dyspnoea or faintness. Applying recent diagnostic criteria including DSM-III-R and DSM-IV, epidemiological studies have reported annual prevalence at 2.3%, 2.2% and 2.7%. One-third to one-half of patients with panic disorder in community samples is also diagnosed to have agoraphobia.
Two broad categories of treatment have been shown to be effective in treating panic disorder; one is pharmacotherapy including benzodiazepines and antidepressants, and the other is psychotherapy including behaviour therapy and cognitive behaviour therapy.
Recent guidelines recommended selective serotonin reuptake inhibitors (SSRIs) as the first-line pharmacological treatment and argued that its efficacy was comparable to psychotherapy alone. However, the most recently published systematic review has shown that the combined antidepressant plus psychotherapy was superior to either monotherapy in the short term, and also superior to antidepressant alone but was as good as psychotherapy alone in the long term.
Benzodiazepines have been the most frequently prescribed medication for patients with panic disorder. There are some advantages to treatment with benzodiazepines in that they lead to effects on panic attacks earlier with milder adverse effects than antidepressants. Nevertheless, the use of benzodiazepines has been associated with sedation, reduced coordination, cognitive impairments, increased accident proneness and development of dependence, and it has been reported that a rebound of panic attacks can occur during taper.
Psychotherapy has also been reported to be effective in treating panic disorder and is a potential alternative to the use of benzodiazepines without any adverse drug effects. On the other hand, psychotherapy has been said to need longer time to show its effects on panic disorder than benzodiazepines.
A benzodiazepine and psychotherapy are widely used together in practice. In a specialized clinic for cognitive-behaviour therapy, over three quarters of the patients were given benzodiazepines. However, little evidence exists so far for any additional benefit to combination therapy and, if so, whether the benefit is worth the extra cost of combining two treatments. Furthermore, some observational studies suggested that benzodiazepines actually interfered with cognitive-behavioral interventions, while others suggested otherwise. We therefore need stronger evidence to get a more precise estimate of their efficacy and safety.
The primary objective of the present systematic review is to comprehensively search for and synthesize the best evidence on the combined psychotherapy plus benzodiazepines in comparison with either treatment alone for panic disorder with or without agoraphobia, in both the short- and long-term.
Abstract and Background
Abstract
Background: The efficacy of combined psychotherapy and benzodiazepine treatment for panic disorder is still unclear despite its widespread use. The present systematic review aims to examine its efficacy compared with either monotherapy alone.
Methods: All randomised trials comparing combined psychotherapy and benzodiazepine for panic disorder with either therapy alone were identified by comprehensive electronic search on the Cochrane Registers, by checking references of relevant studies and of other reviews, and by contacting experts in the field. Two reviewers independently checked eligibility of trials, assessed quality of trials and extracted data from eligible trials using a standardized data extraction form. Our primary outcome was "response" defined by global judgement. Authors of the original trials were contacted for further unpublished data. Meta-analyses were undertaken synthesizing data from all relevant trials.
Results: Only two studies, which compared the combination with behaviour (exposure) therapy, met our eligibility criteria. Both studies had a 16-week intervention. Unpublished data were retrieved for one study. The relative risk for response for the combination was 1.25 (95%CI: 0.78 to 2.03) during acute phase treatment, 0.78 (0.45 to 1.35) at the end of treatment, and 0.62 (0.36 to 1.07) at 6-12 months follow-up. Some secondary outcomes hinted at superiority of the combination during acute phase treatment.
One study was identified comparing the combination to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98), 3.39 (1.03 to 11.21, statistically significant) and 2.31 (0.79 to 6.74) respectively. The superiority of the combination was observed on secondary outcomes at all the time points. No sub-group analyses were conducted due to the limited number of included trials.
Conclusion: Unlike some narrative reviews in the literature, our systematic search established the paucity of high quality evidence for or against the combined psychotherapy plus benzodiazepine therapy for panic disorder. Based on limited available published and unpublished data, however, the combined therapy is probably to be recommended over benzodiazepine alone for panic disorder with agoraphobia. The combination might be superior to behaviour therapy alone during the acute phase, but afterwards this trend may be reversed. We know little from these trials about their adverse effects.
Background
Panic disorder is characterized by the repeated occurrence of unexpected panic attacks, i.e. abrupt strong fears with anticipation of death, often accompanied by somatic symptoms such as palpitations, dyspnoea or faintness. Applying recent diagnostic criteria including DSM-III-R and DSM-IV, epidemiological studies have reported annual prevalence at 2.3%, 2.2% and 2.7%. One-third to one-half of patients with panic disorder in community samples is also diagnosed to have agoraphobia.
Two broad categories of treatment have been shown to be effective in treating panic disorder; one is pharmacotherapy including benzodiazepines and antidepressants, and the other is psychotherapy including behaviour therapy and cognitive behaviour therapy.
Recent guidelines recommended selective serotonin reuptake inhibitors (SSRIs) as the first-line pharmacological treatment and argued that its efficacy was comparable to psychotherapy alone. However, the most recently published systematic review has shown that the combined antidepressant plus psychotherapy was superior to either monotherapy in the short term, and also superior to antidepressant alone but was as good as psychotherapy alone in the long term.
Benzodiazepines have been the most frequently prescribed medication for patients with panic disorder. There are some advantages to treatment with benzodiazepines in that they lead to effects on panic attacks earlier with milder adverse effects than antidepressants. Nevertheless, the use of benzodiazepines has been associated with sedation, reduced coordination, cognitive impairments, increased accident proneness and development of dependence, and it has been reported that a rebound of panic attacks can occur during taper.
Psychotherapy has also been reported to be effective in treating panic disorder and is a potential alternative to the use of benzodiazepines without any adverse drug effects. On the other hand, psychotherapy has been said to need longer time to show its effects on panic disorder than benzodiazepines.
A benzodiazepine and psychotherapy are widely used together in practice. In a specialized clinic for cognitive-behaviour therapy, over three quarters of the patients were given benzodiazepines. However, little evidence exists so far for any additional benefit to combination therapy and, if so, whether the benefit is worth the extra cost of combining two treatments. Furthermore, some observational studies suggested that benzodiazepines actually interfered with cognitive-behavioral interventions, while others suggested otherwise. We therefore need stronger evidence to get a more precise estimate of their efficacy and safety.
The primary objective of the present systematic review is to comprehensively search for and synthesize the best evidence on the combined psychotherapy plus benzodiazepines in comparison with either treatment alone for panic disorder with or without agoraphobia, in both the short- and long-term.