Long Term Efficacy of CBT?

I get email updates from several places I consider reasonably reputable, like NEJM, that have lists of new and interesting articles. I consider those kinds of updates helpful ways of staying current. I also get other kinds of email updates that feel more like ads, or infomercials, like this one, from Psychiatric News Alert:

Study Finds Long-Term Benefits of CBT for Patients With Treatment-Resistant Depression

Patients with treatment-resistant depression who receive cognitive-behavioral therapy (CBT) in addition to antidepressants over several months may continue to benefit from the therapy years later, according to a study in Lancet Psychiatry...

“Our findings provide robust evidence for the effectiveness of CBT given as an adjunct to usual care that includes medication in reducing depressive symptoms and improving quality of life over the long term,” the study authors wrote. “As most of the CoBalT participants had severe and chronic depression, with physical or psychological comorbidity, or both, these results should offer hope for this population of difficult-to-treat patients.”


You can link to the Lancet Study, Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial, by Wiles et al,  here. It's full text.


In brief:

Background
Cognitive behavioural therapy (CBT) is an effective treatment for people whose depression has not responded to antidepressants. However, the long-term outcome is unknown. In a long-term follow-up of the CoBalT trial, we examined the clinical and cost-effectiveness of cognitive behavioural therapy as an adjunct to usual care that included medication over 3–5 years in primary care patients with treatment-resistant depression.

Methods
CoBalT was a randomised controlled trial done across 73 general practices in three UK centres. CoBalT recruited patients aged 18–75 years who had adhered to antidepressants for at least 6 weeks and had substantial depressive symptoms (Beck Depression Inventory [BDI-II] score ≥14 and met ICD-10 depression criteria). Participants were randomly assigned using a computer generated code, to receive either usual care or CBT in addition to usual care. Patients eligible for the long-term follow-up were those who had not withdrawn by the 12 month follow-up and had given their consent to being re-contacted. Those willing to participate were asked to return the postal questionnaire to the research team. One postal reminder was sent and non-responders were contacted by telephone to complete a brief questionnaire. Data were also collected from general practitioner notes. Follow-up took place at a variable interval after randomisation (3–5 years). The primary outcome was self-report of depressive symptoms assessed by BDI-II score (range 0–63), analysed by intention to treat. Cost-utility analysis compared health and social care costs with quality-adjusted life-years (QALYs)...


They took an old study, with subjects who had taken antidepressants for at least 6 weeks and had substantial depression symptoms characterized by a BDI-II score of at least 14, and followed up with a questionnaire and GP notes. Primary outcome was self-report of depressive symptoms assessed by BDI-II score. They also did a cost analysis.


Findings
Between Nov 4, 2008, and Sept 30, 2010, 469 eligible participants were randomised into the CoBalT study. Of these, 248 individuals completed a long-term follow-up questionnaire and provided data for the primary outcome (136 in the intervention group vs 112 in the usual care group). At follow-up (median 45·5 months [IQR 42·5–51·1]), the intervention group had a mean BDI-II score of 19·2 (SD 13·8) compared with a mean BDI-II score of 23·4 (SD 13·2) for the usual care group (repeated measures analysis over the 46 months: difference in means −4·7 [95% CI −6·4 to −3·0, p<0·001]). Follow-up was, on average, 40 months after therapy ended. The average annual cost of trial CBT per participant was £343 (SD 129). The incremental cost-effectiveness ratio was £5374 per QALY gain. This represented a 92% probability of being cost effective at the National Institute for Health and Care Excellence QALY threshold of £20 000.


Follow-up was a median of 45.5 months, at which point, the CBT group had a mean BDI-II of 19.2, and the control group a mean BDI-II of 23.4


Interpretation
CBT as an adjunct to usual care that includes antidepressants is clinically effective and cost effective over the long-term for individuals whose depression has not responded to pharmacotherapy. In view of this robust evidence of long-term effectiveness and the fact that the intervention represented good value-for-money, clinicians should discuss referral for CBT with all those for whom antidepressants are not effective.


Note that "individuals whose depression has not responded to pharmacotherapy," were taking antidepressants for 6 weeks. The study states later that, "This definition of treatment-resistant depression was inclusive and directly relevant to primary care."

Let's look at the details. I'll start by stating that I'm not going to consider the cost effectiveness, because I don't know how. And it may be that even if the clinical effects turn out to not be impressive (spoiler!), the treatment may be worthwhile from a financial standpoint.

At the start of the current study, all patients were taking antidepressants, and were randomized to 12-18 sessions of CBT, or usual care from their GPs. I find this confusing. It seems like medication ought to be a confounder, since depression is cyclic to begin with and people respond to medications at variable rates. Also, if you consider these patients to be treatment resistant, why continue them on antidepressants?

I also find what they did with the outcome measures confusing:

The primary outcome was self-report of depressive symptoms assessed by BDI-II score (range 0–63). Secondary outcomes were response (≥50% reduction in depressive symptoms relative to baseline); remission (BDI-II score <10); quality of life (Short-Form health survey 12 [SF-12]); and measures of depression (PHQ-9) and anxiety (Generalised Anxiety Disorder assessment 7 [GAD-7])...

The primary outcome for the main trial was a binary response variable; for this follow-up, the primary outcome was specified as a continuous outcome (BDI-II score) to maximise power. The change in the specification of the primary outcome for the long-term follow-up was made at the time the request for additional funding was submitted to the funder (Nov 6, 2012).

Does this mean they changed the primary outcome? In the original CoBalT trial, "The primary outcome was response, defined as at least 50% reduction in depressive symptoms (BDI score) at 6 months compared with baseline." Did the present study start out using response, and then switch to change in BDI-II score after the fact, which we all know is a no-no? They're claiming they changed it when they requested funding for the current study, but is that before or after they had established their primary outcome measure?

Or did the current study start with change in BDI-II score as the primary outcome measure, and is that okay? In other words, if you're basing your current study on a previous study, is it valid to establish your protocol with a different outcome measure than the original study? I don't know.

Moving on. The study makes a lot of claims about secondary outcomes, and whether or not subjects were still taking antidepressants, but I'm restricting myself to thinking about the primary outcome, and the BDI-II measures are as follows:

The effect size, according to this chart, is 0.45, which is on the low side of moderate. I don't know how they did their computation, but when I used 1BoringOldman's spreadsheet (see this post), I got a Cohen's d effect size of 0.31, which is low.

I'm not sure how this constitutes "Robust evidence." I'm also not sure what's robust about a mean BDI-II of 19.2, when by their definition, a BDI-II score of more than 14 is considered "Substantial depressive symptoms."

Look. I'm not a big fan of CBT, but I'm willing to consider it as a useful treatment if you show me good data. Just don't go hyping your at-best-mediocre data like it's amazing. But of course, Psychiatric News is a product of the APA.

Does Talk Therapy Work?

Take a look at the article in today's NY Times, Effectiveness of Talk Therapy Is Overstated, a Study Says.  

It's about a study published in PLOS one,

Does Publication Bias Inflate the Apparent Efficacy of Psychological Treatment for Major Depressive Disorder? A Systematic Review and Meta-Analysis of US National Institutes of Health-Funded Trials

Well, it's all very interesting. They were trying to look at publication bias in studies about talk therapy, and they found it. Of the 57 studies that met their inclusion criteria, 13 were never published-they learned about them by contacting the study authors.

And by their estimation, talk therapy is 25% less effective than previously believed.

The study looked at NIH grants between 1972 and 2008, and tried to match the grants to published studies. They were pretty thorough in their search terms:

(1) “depression” (depression, depressive, major depressive disorder, mood disorder, affective disorder, melancholic, melancholia) and (2) “psychological treatment” (cognitive therapy, behavior therapy, behavioral therapy, interpersonal therapy, psychodynamic therapy, dynamic therapy, humanistic therapy, therapy, supportive therapy, experiential therapy, [self-] control therapy, [problem-] solving therapy, [supportive-] expressive therapy, family therapy, group therapy, marital therapy, couples therapy, aversive therapy, exposure therapy, psychotherapy, psychotherapies, psychotherapeutic, counseling, disease management, psychoanalytic, behavioral activation, cognitive behavioral analysis system, desensitization, relaxation techniques, and progressive muscle relaxation). 

Of note to me is that they included "psychoanalytic", but not "psychoanalysis".

Inclusion criteria were:

(1) a randomized clinical trial examining (2) psychological treatment for (3) acute depression in (4) adults

This is a diagram of how they selected studies:

It bothers me a little that they started out with 4073 studies, and ended up with 57. But they seem to have been pretty thorough in how they went about it.

This is the table of the 57 varieties of studies they looked at:

Sorry,  I meant:

Of note again to me is that 5 of the studies are in Short Term Psychodynamic/Psychoanalytic Psychotherapy (STPP).


I'm not terribly surprised by their results. I don't put that much stock in the long-term effects of short term therapy. You may recall my post, Analytic Evidence, probably worth a shifty in this context. I've never been a big fan of CBT, except in very specific presentations, but admittedly, I think my CBT training was inadequate.

What I don't like about the study, and the Times article, is the overall message to the uninitiated. These were short-term treatments, and they were heterogeneous in type. These limitations are not addressed in the discussion section of the study. So the message is that all "Talk Therapy" doesn't work as well as we thought, with no differentiation between type or duration of therapy. And this is misleading and may keep people from seeking help.

Analytic Evidence

One of my goals, or maybe wishes, in writing this blog, is to educate a wider audience about psychoanalysis. Let's face it, analysis is, at best, passe. Mostly it's dissed. After all, everyone "knows" there's no evidence that analysis works, but there's lots of evidence that CBT works, so why spend all that time and money in analysis when you could be in and out in 30 sessions?

Just see this article in the NY Times:

As Jeffrey A. Lieberman, chairman of psychiatry at the Columbia University College of Physicians and Surgeons, makes clear in his chatty, expert, sometimes scathing but ultimately upbeat account of the history of psychiatry, the evidence, quite simply, doesn’t exist.

Maybe analysis was cool back in the 50's and 60's, when everyone smoked during sessions, and the analyst had a beard and a deep-voiced German accent and was a blank screen who only made comments about oedipal conflict. It's fun to watch in Woody Allen movies, but really, it's just a silly, archaic modality that thinks penis envy is the cause of everyone's problems, and now functions only as a narcissistic indulgence for the wealthy.

I once mentioned to a colleague I had just met that at certain hospitals, psychiatrists are not permitted to wear white coats because it makes the patients anxious. His response was, "That's just analytic bullshit!" I guess to most people, analysis qualifies as its own special category of bullshit.

Well, there is evidence that analysis works. Not only that it works, but that it works better than meds or CBT. I highly encourage readers to watch a 35 minute video on YouTube entitled, The Case for Psychoanalysis, Version 4, by John Thor Cornelius, a psychiatrist and psychoanalyst from California, who took on the challenge of convincing residents at UC Davis, who had been taught otherwise, that there is evidence for the usefulness of psychoanalysis. Obviously, he's made 3 earlier versions of the video, and he updates as new evidence becomes available. But I'm going to use highlights of the video (with his permission), and include other evidence, in this post.

Cornelius looked at effect size in meta-analyses of meds, CBT, and psychoanalytic psychotherapy, which he uses as a stand-in for analysis. The difference between analysis and analytic psychotherapy is something I'll get to in another post. Maybe. There's a lot of literature on it. For now, it'll have to be an adequate place-holder, and obviously, for my purposes, this is one of the limitations of his presentation.

Just quickly, effect size is the difference between treatment groups, expressed in standard deviations. Roughly speaking, a large effect size is 0.8, medium is 0.5, and small is 0.2. So, for example, if the effect size of A v. B is 0.8, then A did 0.8 of a standard deviation better than B, and this is considered a large effect.

 First, Cornelius looked at effect sizes at the ends of studies:

Erick H Turner, MD, Annette M Matthews, MD, Eftihia Linardatos, BS, Robert A Tell, LCSW, and Robert Rosenthal, PhD. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. NEJM 2008; 358:252-260 January 17, 2008.
Butler, AC, Chapman, JE, Forman EM, & Beck, AT. (2006). The empirical status of cognitive-behavioral therapy: A review of meta-analyses. Clinical Psychology Review, 26 (1), 17-31.
Abbass AA, Hancock JT, Henderson J, Kisely S, Short-term psychodynamic psychotherapies for common mental disorders. Cochrane Database Syst Rev. 2006;4:CD004687.
Maat S, De Jonghe F, Schoevers R, Dekker J. The effectiveness of long-term psychoanalytic therapy: a systematic review of empirical studies. Harv Rev Psychiatry. 2009;17(1):1-23.

You'll notice antidepressants aren't great, and CBT for chronic pain isn't either, but everything else does okay.

Then he looked at long-term follow-up, and this is what he found.

For antidepressants:

For Psychotherapy, there is evidence that its benefits endure and increase over time (Psychodynamic Psychotherapy Research: Evidence-Based Practice and Practice-Based Evidence (Current Clinical Psychiatry) [Kindle Edition]Raymond A. Levy (Editor), J. Stuart Ablon (Editor), Horst Kächele (Editor)):

Leichsenring F, Rabung S. Effectiveness of long-term psychodynamic psychotherapy: a meta-analysis. J Am Med Assoc. 2008;300:1551-65.

MBT is Mentalization Based Treatment, an 18 month psychoanalytic partial hospitalization protocol for borderline personality disorder. 

Bateman A, Fonagy P. Randomized controlled trial of outpatient mentalization-based treatment versus structured clinical management for borderline personality disorder. Am J Psychiatry. 2009;165:556-9.

As for CBT, some of the results fall under Steps 2, 3, and 4 of the STAR-D trial, which had CBT arms. But here are some more results to consider:

40-50,000 patients per year for 5 years, $500 million dollars, and no effect of CBT. Those numbers big enough for you?


Next up, head to head comparison of psychoanalysis (PA), psychodynamic psychotherapy (PD), and CBT.

Comparison of cognitive-behaviour therapy with psychoanalytic and psychodynamic therapy for depressed patients – A three-year follow-up study (Z Psychosom Med Psychother 58/2012, 299–316), by Huber et al, is a prospective study of 100 patients diagnosed with unipolar depression and randomized into the three groups. I'm not including the studies this one follows-up on because this post is already too long.

"...mean duration of PA was 39 months (range 3–91) or 234 sessions (range 17–370), of PD was 34 months (range 3–108) or 88 sessions (range 12–313), and of CBT was 26 months (range 2–78) or 45 sessions (range 7–100); minimal values are due to the intent-to-treat approach."

PA was practiced at a frequency of 2-3 sessions per week, on the couch. PD was once a week, sitting up. And CBT was once a week.

There were 21 therapists, all past training, with mean duration of practice 15 years. 7 did CBT, and 14 did PA or PD, and there was no significant difference in respective training, expertise, and experience.

Raters were blind to treatment modality. They used a 3 year follow-up period to account for the naturally fluctuating course of depression. Treatment fidelity was also assessed.

"Outcome measures were the Beck Depression Inventory and Global Severity Index for measuring symptoms, the Inventory of Interpersonal Problems and the Social Support Questionnaire for measurement of social-interpersonal functioning, and the INTREX Introject Questionnaire for measuring personality structure."

I'm leaving out a lot of the methodological details, but I did want to give you the general sense that the study was conducted in a rigorous way. And these were the results:

"...at three-year follow-up, rate of remission from depressive symptoms was 83% in the PA group, 68% in the PD group, and 52% in the CBT group. When controlling age and gender, the odds of remission were significantly greater in the PA group as compared to the CBT group, with odds ratio (OR) = 4.79, 95% CI [1.29 to 17.74], and did not differ between the PD and CBT groups, with OR = 2.06, 95% CI [0.60 to 7.10]."

More generally, they found, "significant outcome differences between psychoanalytic therapy and cognitive-behaviour therapy in depressive and global psychiatric symptoms, partly social-inter- personal and personality structure at three-year follow-up. Psychodynamic therapy was superior to cognitive-behaviour therapy in the reduction of interpersonal problems."

In the discussion section, the authors were pretty good at describing the limitations of the study. They also addressed the question of a dose effect. We're talking 45 sessions of CBT vs. 88 sessions of PD vs. 234 sessions of PA. This is a fair question to ask, i.e., would 234 sessions of CBT have been as effective as the same 234 sessions of PA? However, the CBT lasted, on average, 26 months, while the PA lasted 39 months, only about a year longer than the CBT. At the rate of 1 session a week, or roughly 4 sessions a month, a CBT of 234 sessions would last for 58.5 months, or about 5 years, 2 years longer than the average psychoanalysis in the study lasted.

This was pretty farschlepped, but I hope you can see that there is some evidence that psychoanalysis is effective. Jeez, Dr. Lieberman, do your homework!

NY Times: Why Doctors Need Stories

I just want to link to an article by Peter Kramer, published today in the NY Times:

Why Doctors Need Stories

It's about the role of the case vignette, and how it shouldn't be discounted in the face of evidence based medicine. It also reflects my personal opinion about the significant limits of CBT, despite all its hype.

I submitted this comment:

As a psychiatrist and psychoanalyst, I applaud Dr. Kramer's embrace of "the story". But I don't think case vignettes need to be limited to the role of adjunct to evidence based medicine. Case vignettes actually do supply statistical evidence. A research group from the University of Ghent, in Belgium, specializes in Meta-Synthesis (as opposed to meta-analysis), in which they mine the data generated by a large collection of single case vignettes. You can check out their website: singlecasearchive.com, where you can search for different parameters within papers that have already been published.

You may recall my mention of this topic in a post from last January, The Rest of the Meeting. Feel free to recommend my comment (under the name, Physician NYC-not sure how that happened) from 2:14pm on Sunday the 19th.

It's All in the Spin

Another email from the APA today, oh joy:

CBT More Efficacious Than Other Psychological Interventions for Positive Symptoms of Psychosis.

This was based on the article: Psychological Interventions for Psychosis: A Meta-Analysis of Comparative Outcome Studies, published February 14th on AJP in Advance.

CBT was compared with supportive counseling, social skills training, psycho-education, cognitive remediation and befriending in 48 trials.

Results  Cognitive-behavioral therapy (CBT) was significantly more efficacious than other interventions pooled in reducing positive symptoms (g=0.16). This finding was robust in all sensitivity analyses for risk of bias but lost significance in sensitivity analyses for researcher allegiance, which suffered from low power. Social skills training was significantly more efficacious in reducing negative symptoms (g=0.27). This finding was robust in sensitivity analyses for risk of bias and researcher allegiance. Significant findings for CBT, social skills training, and cognitive remediation for overall symptoms were not robust after sensitivity analyses. CBT was significantly more efficacious when compared directly with befriending for overall symptoms (g=0.42) and supportive counseling for positive symptoms (g=0.23).

The APA seems rather pleased with itself about this result. The email even linked to a news article, CBT Addresses Most-Debilitating Symptoms in Chronic Schizophrenia.

A new cognitive-behavior therapeutic strategy [Recovery Oriented Cognitive Therapy (CT-R)] is helping patients overcome major obstacles to their recovery, especially the negative symptoms...that are considered to be the most intransigent and disabling for patients with schizophrenia. The strategy has been implemented throughout the Philadelphia public mental health system and in Georgia

You'd think they'd at least cross check their own links. CT-R is especially helpful with negative symptoms, but the meta-analysis demonstrated that social skills training was significantly more efficacious than CBT in reducing negative symptoms.

The email caught my eye because I had just finished reading this month's Carlat Report, in which there was an article entitled, "CBT for Schizophrenia: Is Talk Cheap?", which, in turn, references, "Cognitive-behavioural therapy for the symptoms of schizophrenia: systematic review and meta-analysis with examination of potential bias," published in the British Journal of Psychiatry.

THIS study looked at 50 trials of CBT for schizophrenia, and found that when raters were blinded to the type of treatment provided, effect size of CBT relative to placebo dropped from 0.62 in unblinded studies, to 0.15 in blinded studies, for overall symptoms. For positive symptoms, the drop was from 0.57 to 0.08. 
Pooled effect sizes were 0.33 for overall symptoms, 0.25 for positive symptoms, and 0.13 for negative symptoms. 
Not sure why they didn't describe the difference between unblinded and blinded studies for negative symptoms. Maybe because the pooled effect size was so low to begin with.

It's kind of like what I wrote about the APA excitement about the meeting in May. Pick some highlight, maybe Alan Alda, talk about how great the meeting will be, and ignore all the annoying little facts that might put a damper on things.