This study evaluates the efficacy of clonazepam, a benzodiazepine used for treating anxiety linked to social phobia. This disorder is characterized by an intense, persistent fear of judgment by others, leading to avoidance of social situations.

Benzodiazepines enhance the effects of GABA, an inhibitory neurotransmitter that restores us to a state of calm, following the release of the excitatory neurotransmitters such as noradrenaline. Benzodiazepines enhance the work of GABA by increasing the opening of chloride channels in the GABA_A receptors. When these channels are open, they allow negatively charged chloride ions to rush into the cell. This inhibits the excitatory effects of other neurotransmitters making it less likely that the cell will release an action potential. Feelings of anxiety are replaced with calm and we regain a sense of control.

This study evaluated the efficacy of clonazepam in targeting specific aspects of social phobia, including fear, avoidance, and effects on daily functioning.

This experiment used a double-blind, independent samples design with random allocation to groups. The independent variable was whether the participants took clonazepam (n=39) or an identical-looking placebo (n=36). All 75 participants were outpatients with a diagnosis of social phobia made within the last 6 months. None had symptoms of comorbid depression, panic disorder, or a history of alcohol or substance abuse within the past 12 months.  Participants abstained from taking any other medications for two weeks prior to the study, controlling any extraneous effects of any other substances that might interfere with the effects of the clonazepam. On the first three days of the trial, people took a daily dose of 0.25 mg of clonazepam or the placebo, increasing gradually to a maximum of 3 mg over 25 days. If adverse side effects arose, lower doses were maintained. The average clonazepam intake was 2.4 mg a day.

The severity of the participants' symptoms were measured at the start of the study and then every two weeks until week 10 using several different scales. The Clinical Global Impressions-Severity of Illness Scale (CGI-S) was used to measure the severity of symptoms.  The scale was completed by experienced clinicians.  The rating was on a 7-point scale where 1 is not ill at all and 7 is among the most extremely ill patients.

Following drop-out, participants’ last scores were carried forward, increasing the sample size and thus the power of subsequent statistical tests. 

The percentages of responders to treatment versus non-responders were reported. Clinically-significant responses were operationalized as final CGI scores of 1 or 2 (‘very much improved’ or ‘much improved’). Scores between 3 and 5 (minimal improvement, no improvement, or worse) were classed as non-responders.

The response rate for clonazepam was 78.3% and 20% for the placebo group. A chi-squared showed this result to be highly significant, (p < 0.0001).

People who took clonazepam improved more than the control group. Clinically significant improvements were apparent even from one week and overall, the clonazepam group’s CGI-S scores reduced by 51.4% compared with 20% in the placebo group.

On the downside, the clonazepam group experienced more side effects than the placebo group, e.g. sexual dysfunction (23% versus 3%) unsteadiness (28% versus 0%), and dizziness (29% versus 0%), while other side effects included blurred vision and a bad taste in the mouth.

Overall, the researchers concluded that clonazepam can elicit “early and sustained therapeutic effects” for people with social phobia and that the effects were evident across the full range of symptoms. 

Strengths of this study include the double-blind, randomized design which increases internal validity. This means the findings can be reported with greater confidence, that is - the differences in improvement can be attributed to the clonazepam as opposed to some other variable. The two groups were also well matched in terms of demographic factors including gender, age, marital status, age of onset, and severity of symptoms at the start of the trial, further increasing internal validity.

The double-blind design meant neither the participants nor the researchers knew who had taken the real drug and who had taken the placebo. Since participants in both groups thought they might be taking the real drug, both groups would have had a mild expectancy of improvement. This means any difference in the degree of improvement made by people in the experimental group compared with the control group must have been due to the active ingredient in the drug, rather than the positive effects of knowing they were taking medication.

Limitations of the research include the short term nature of the trial. It was not possible to monitor whether symptoms returned following negative life events or whether the placebo group may have shown more improvement over time. It would have been interesting to see how tolerance and side effects changed over time and whether this affected compliance.

Further limitations include poor generalisability to non-white populations. There was only one African American participant in the sample and the researchers do not comment on the ethnicity of the remaining Caucasian sample. This is critical as people from ethnic minority backgrounds are overrepresented in mental health statistics yet less likely to be receiving treatment.

Attrition was relatively high (25% in each group by week 10) and those who dropped out experienced less improvement than the completers; it would be interesting to know more about these treatment-resistant non-completers, as there may be individual differences in terms of the causes of anxiety disorders and the findings may therefore not be generalizable to everyone who has an anxiety disorder.