COMLEX USMLE Board Review Blogger

• How common are anxiety disorders?
• What psychological treatments have empirical support?
• What recovery rates can be achieved with these treatments?
• How enduring are their effects?
• Is there value in combining psychological treatments with medication?

Psychological treatments can be delivered in a variety of formats. This paper restricts itself to the traditional, and most extensively researched, format of face-to-face contact with a fully qualified therapist. For most anxiety disorders the therapy sessions are once weekly for 60-90 minutes spread over a period of 8-20 weeks, with homework assignments in between. However, in specific phobias, the strongest outcomes have been obtained with a single, long (3-5 hour) session with a therapist, followed by a briefer follow-up session a week or so later.

What treatments have empirical support?

The gold standard for determining clinical effectiveness is the randomized controlled trial (RCT) in which the treatment to be evaluated is compared with various control conditions. Patients are randomly allocated to the treatment under investigation or the control conditions in order to ensure that any difference in outcome is not due to patient characteristics. When evaluating psychological treatments for anxiety disorders, three control conditions are of particular interest.

1) No treatment. This is usually achieved by randomizing some patients to immediate treatment and some to treatment after a wait period (Wait List control).

2) An equally credible, alternative psychological treatment. This condition is included to determine whether at least part of the effectiveness of the psychological treatment is due to procedures that are specific to that particular treatment, as opposed to non-specific procedures that would be common to any reasonably delivered psychological intervention. For example, seeing a warm, empathic therapist who expresses interest in your problems and generates hope. This is the psychological equivalent of the placebo pill in a trial evaluating the effects of a drug.

3) An evidence based medication. Some medications (mainly anti-depressants) are effective in anxiety disorders. If psychological treatments are to be offered as an alternative, one would ideally want to show that the psychological treatments are at least as effective as medication.

There are 6 anxiety disorders. Following a review of published randomized controlled trials, NICE has issued clinical guidance for four of the anxiety disorders (panic disorder², generalized anxiety disorder², posttraumatic stress disorder³, obsessive-compulsive disorder⁴). Each guidance indicates that cognitive-behaviour therapy (CBT) is an effective treatment. In each disorder, published RCTs indicate that CBT has passed all three of the comparisons mentioned above (i.e. superior to no-treatment, superior to an equally credible alternative psychological treatment and at least as effective as medication). No other psychological treatment was considered by NICE to be effective in anxiety disorders in general. However, Eye Movement Desensitization Reprocessing (which some people argue is a form of CBT) was supported in posttraumatic stress disorder.

NICE has not yet commissioned guidance for the two remaining anxiety disorders (social phobia and specific phobia) or for a closely linked condition that is common in primary care (hypochondriasis/severe health anxiety). However, the RCT findings for each of these disorders are very similar to those obtained in the four disorders that are currently covered by NICE guidance. In particular, for each disorder there are RCTs that show that CBT is: superior to no treatment^5-9, superior to a similarly credible alternative psychosocial treatment^{5 7 10 11}, and at least as effective as medication^12-16. No other psychological treatment approach for these disorders has been supported in randomized controlled trials.

Although non-CBT approaches have not yet received significant support in RCTs, a recent non-randomized comparison between CBT and two other therapies has been interpreted by some media commentators as evidence that non-CBT approaches are as effective as CBT. This interpretation is unwarranted. In the study¹⁷ NHS therapists working in primary and secondary care were invited to use a standardized symptom questionnaire (the CORE-OM) with their patients and to submit the questionnaires to a central database. The therapists identified anxiety and depression as patients’ most common problems, followed by interpersonal difficulties. For the patients whose pre-treatment and post-treatment data were included the database there were few differences in outcome between CBT, person centred therapy (PCT) and psychodynamic and/or psychoanalytic therapy (PDT). However, this finding cannot be taken as evidence of therapeutic equivalence because several methodogical problems mean the study could easily have obscured real differences. The main methodological problems are: 1) Unrepresentativeness of the sample. It appears that less than 10% of therapists cases were included in the database and there is evidence (cited by the authors) that included cases are likely to have had better outcome. 2) Differences in settings. PCT and PDT patients were largely in primary care counseling services, whereas CBT was often in secondary care. On average, secondary care patients should be more likely to have failed previous treatments and less likely to show natural recovery. 3) Failure to control for the effects of concurrent medication. Approximately half the patients were taking a psychotropic medication that could be partly responsible for the observed improvement. 4) No control for natural recovery (which is common in recent onset cases of anxiety and depression). 5) No information on whether the treatments were properly administered. In particular, it is not known whether the therapists were appropriately trained in the therapies they reported using.

What recovery rates can be achieved with CBT?

Although RCTs have provided strong support for the effectiveness of CBT in all the anxiety disorders, it is important to realize that CBT is a broad class of therapies. There are several different CBT programs, some specifically tailored to particular anxiety disorders. RCTs comparing different CBT approaches are relatively rare. However, when these have been conducted, evidence of differential effectiveness has sometimes been obtained^{5 7 18 19}. Table 1 shows the best recovery rates that have been obtained with CBT programs in the different anxiety disorders. A CBT programme needs to have been supported in at least two RCTs in order to be included in the table. Where different CBT programs have reported similar recovery rates, programs developed by UK clinicians are selected as it is likely to be easier to arrange NHS training in these programs. Recovery is defined as no longer meeting diagnostic criteria for the relevant disorder or, if this information is not available, meeting strict criteria for “high end-state functioning” or “reliable and clinically significant change”. Recovery rates are “intention-to-treat” with any patients who dropped out of therapy without contributing data being assumed to have failed to recover. Controlled effect sizes refer to the comparison between treatment and no treatment (wait list) and are computed with the following formula: controlled effect size = (mean at post treatment minus at post wait)/pooled standard deviation.

Table 1

Anxiety Disorder	Type of CBT	Recovery Rate	Controlled Effect Size
Panic Disorder	Cognitive therapy18 20	75%	2.9
Posttraumatic Stress Disorder	Cognitive therapy21 22	71% 79%	2.2 (chronic PTSD) 1.3 (recent PTSD)
Social Phobia	Cognitive therapy5 12	76%	2.6
Generalized anxiety disorder	CBT23 24	69%	1.7
Obsessive-compulsive disorder	Exposure + RP4 25 26	49%	1.6
Specific Phobias	Exposure (most), Applied Tension (only blood-injury)27-29	81%	2.7
All anxiety & related disorders	Mean	71%	2.1

Controlled effect sizes of greater than 0.8 are considered large. Inspection of Table 1 reveals that the in all the anxiety disorders the leading forms of CBT achieve effect sizes that are substantially higher than 0.8. In addition, in each disorder half or more of the patients who are given the treatments recover.

How durable are the effects of CBT?

Randomized controlled trials of psychological treatments usually include follow-up assessments. For each of the CBT programmes listed in Table 1, one or two year follow-ups have been reported. Patients have either maintained their therapy gains ^{5 8 12 18 20 22 23 30} or shown some further improvement²⁴. The Follow-ups are naturalist, so it would be possible for patients to seek some further treatment during the follow-up period. Investigators have not always enquired about such extra treatment. However, when they have, the rates have been low^{5 18} for the leading treatments but, perhaps unsurprisingly, have been higher for the treatments that were less effective initially. For example, in social phobia, Clark et al⁵ found that cognitive therapy was more effective than exposure therapy initially and that patients who received either treatment maintained their gains when reassessed one year later. However, during the follow-up year only 6% of cognitive therapy patients had any further treatment, whereas 44% exposure therapy had some form of additional treatment.

Is it beneficial to combine medication with CBT?

Several anti-depressants and anxiolytics have been shown to have beneficial effects in anxiety disorders. This prompts the question: Would the outcome of CBT be improved if it were routinely combined with such medications? Perhaps surprisingly, the answer appears to be No. Randomized controlled trials that have compared CBT alone with CBT plus medication have sometimes observed modest short-term benefits from the addition of anti-depressant medication²⁹. However, other studies^31-33 have found that the long-term outcome of combined treatment is worse than for CBT alone. Studies of single treatments have tended to find higher relapse rates after medication alone than after CBT alone^{18 31 34}. It appears that in combined treatment, relapse rates follow those of medication, rather than those of CBT. In view of these findings, starting medication at the same time as CBT is not recommended as a general strategy. However, medication may be added at a later stage if the initial response to CBT has been less that desired.

Although there do not seem to be strong grounds for adding traditional anti-depressants or anxiolytics to CBT, cognitive enhancers, such as d-cycloserine, may be more promising. Cognitive enhancers do not have anxiolytic effects on their own. However, in single doses they have been shown to enhance emotional learning in animals. Following from these observations, two human studies^{35 36} have combined d-cycloserine with exposure therapy and have found that it leads to greater improvement in phobic anxiety when compared to exposure therapy plus placebo medication. However, more research is needed to define the safety and utility of cognitive enhancers, especially as their effects decline with repeated administration.

7. Conclusions

1) CBT is an effective treatment for all anxiety disorders when delivered in the traditional format of weekly face-to-face sessions with an appropriately trained therapist.

2) CBT is a specific treatment and is at least as effective as medication.

3) The improvements that are observed with CBT are well maintained at 1-2 year follow-up and tend to be more long lasting that the gains obtained with medication alone.

4) The best CBT programmes for anxiety disorders can achieve recovery in over half the patients who start the treatments (except in obsessive-compulsive disorder where the recovery rate is somewhat lower).

5) Routinely combining medication with CBT is not recommended.

Non-CBT psychological treatments have not demonstrated efficacy in anxiety disorders.

References

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