This is the 5^th in a series of blog posts about the 10^th September SIGN draft guideline day on "Non-pharmacological management of depression."  On the day, the second session was entitled "Effectiveness of Psychological Therapies in Depression 1".  Dr Gary Morrison, Consultant Old Age Psychiatrist from Dumfries, gave the first of this session's talks discussing both Cognitive Behavioural Therapy (CBT) and the associated treatments - Behavioural Activation (BA), Cognitive Analytic Therapy (CAT) and Cognitive Behavioural Analysis System of Psychotherapy (CBASP).  For both CBT and BA, SIGN made grade A recommendations for them as treatment options for depression.  I raised the question as to whether SIGN would be commenting on the training and cost implications of both these therapies appearing equally helpful.  I pointed out that it is likely to be considerably more economic to train BA rather than full CBT therapists - this seems an important point, knowing that there are inadequate numbers of therapists to meet the potential demand for evidence-based psychotherapy treatments.  The response was that commenting on training and cost implications isn't part of SIGN's job.

"No good quality evidence" was identified for CAT as a treatment for depression.  For CBASP, apparently SIGN hadn't turned up the evidence yet.  The key initial CBASP study is clearly the one from 2000 published in the New England Journal of Medicine on the treatment of chronic depression (Keller, McCullough et al. 2000).  This research was impressive - 662 patients across 12 US academic centres entered the intention-to-treat analysis.  All were suffering from forms of chronic depression including chronic major depressive disorder (MDD), or MDD superimposed on dysthymic disorder, or recurrent MDD with incomplete remission between episodes.  They were randomized to CBASP, antidepressant, or CBASP plus antidepressant.  48% of patients on either monotherapy were classified as responders, while 73% on combined therapy responded.  For more details on this study see the Powerpoint slides from a lecture I gave in early 2006 (Hawkins 2006).  A cascade of further analyses and follow-up papers have emerged since.  Interesting examples of such research include the finding that early therapeutic alliance significantly predicted subsequent improvement in depressive symptoms after controlling for prior improvement and 8 prognostically relevant patient characteristics. Patients receiving combination treatment reported stronger alliances with their psychotherapists than patients receiving CBASP alone (Klein, Schwartz et al. 2003).  In this chronically depressed population, CBASP was efficacious for many nonresponders to antidepressant, and conversely antidepressant seemed effective for many CBASP nonresponders (Schatzberg, Rush et al. 2005).  Among those with a history of early childhood trauma (loss of parents at an early age, physical or sexual abuse, or neglect), CBASP alone was superior to antidepressant monotherapy. Moreover, the combination of psychotherapy and pharmacotherapy was only marginally superior to psychotherapy alone among the child abuse cohort (Nemeroff, Heim et al. 2003).  Finally, 82 patients who had responded to acute and continuation phase CBASP were randomized to monthly CBASP or assessment only for 1 year. Significantly fewer patients in the CBASP than assessment only condition experienced a recurrence. The 2 conditions also differed significantly on change in depressive symptoms over time (Klein, Santiago et al. 2004).  All of this work points to an important advance in the treatment of chronic forms of depression.  Unfortunately a large unpublished replication study apparently produced less encouraging results (McCullough 2007) - possibly because the patients involved were struggling with more socioeconomic and literacy problems than in the earlier research.  Despite scanning the emerging literature, there is still no sign of this study having been published - maybe an indication of how negative results can often take longer to come to press.  Jim McCullough's CBASP website gives background details of this later research (see link below) but no results so far.  Rob Durham - one of the SIGN depression guideline development group - is very knowledgeable about CBASP and may well have more up to date information than me on this attempted replication study.  Encouragingly there is further work on CBASP in the pipeline (Wiersma, van Schaik et al. 2008), although it will take quite some time before the outcomes become clear.

Since CBASP is probably the only psychological therapy designed specifically for chronic depression, it may be relevant at this point to highlight and challenge a sentence on page 16 of the SIGN draft guideline's section on ‘Provision of information' which states "Remember that the professionals to whom you talk (GP, consultant, nurse, therapist) are there to help you and that you WILL (sic) get better."  Happily it's certainly true that the majority of people suffering an episode of depression will recover - but sadly not all (Dunner, Rush et al. 2006; Rush, Trivedi et al. 2006; Eaton, Shao et al. 2008).  This sentence should be changed. 

Dunner, D. L., A. J. Rush, et al. (2006). "Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression." J Clin Psychiatry 67(5): 688-95.  [PubMed] 
Eaton, W. W., H. Shao, et al. (2008). "Population-Based Study of First Onset and Chronicity in Major Depressive Disorder." Arch Gen Psychiatry 65(5): 513-520. [Abstract/Full Text] 
Hawkins, J. (2006).  "CBASP: cognitive behavioural analysis system of psychotherapy."  Powerpoint slide presentation.
Keller, M. B., J. P. McCullough, et al. (2000). "A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression." N Engl J Med 342(20): 1462-70.  [Abstract/Free Full Text]
 Klein, D. N., N. J. Santiago, et al. (2004). "Cognitive-behavioral analysis system of psychotherapy as a maintenance treatment for chronic depression." J Consult Clin Psychol 72(4): 681-8.  [PubMed] 
Klein, D. N., J. E. Schwartz, et al. (2003). "Therapeutic alliance in depression treatment: controlling for prior change and patient characteristics." J Consult Clin Psychol 71(6): 997-1006.  [PubMed] 
McCullough, J. P. (2007). Personal communication at 3 day CBASP workshop. Dundee, Scotland. April 9-11.
McCullough, J. P.  Website at http://www.cbasp.org/  Accessed on September 22, 2008.
Nemeroff, C. B., C. M. Heim, et al. (2003). "Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma." Proc Natl Acad Sci U S A 100(24): 14293-6.  [PubMed] 
Rush, A. J., M. H. Trivedi, et al. (2006). "Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report." Am J Psychiatry 163(11): 1905-17.  [PubMed] 
Schatzberg, A. F., A. J. Rush, et al. (2005). "Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not." Arch Gen Psychiatry 62(5): 513-20.  [PubMed] 
Wiersma, J. E., D. J. van Schaik, et al. (2008). "Treatment of chronically depressed patients: a multisite randomized controlled trial testing the effectiveness of 'Cognitive Behavioral Analysis System of Psychotherapy' (CBASP) for chronic depressions versus usual secondary care." BMC Psychiatry 8: 18.   [Abstract/Free Full Text]