Specific and Non-Specific Factors in the Treatment of Depression

A half century ago -- before mental health professionals began arguing over the relative benefits of biological and verbal therapies -- the battle focussed on which methods of psychotherapy worked best. Proponents of psychoanalytic schools, cognitive-behavioral therapy (CBT) and many other verbal treatments argued, as many still do, for the superiority of their approaches. Jerome D. Frank, a professor of psychiatry at Johns Hopkins, was a pioneer in applying objective research techniques to this area. When I became one of his research assistants, he was investigating shared characteristics that might account for the effectiveness of many of these competing therapies. His influential book Persuasion and Healing (1961) greatly broadened the theoretical foundation and operational framework for the approach known as Common Factors Theory.[1] In that book, he repeated the words of the Dodo Bird from Lewis Carroll’s Alice’s Adventures in Wonderland (1865) [2] “Everybody has won and all must have prizes” to embody the idea that all therapies have something to offer based on processes common to all (Table 1).[3, 4]

 Table 1

Table 1

Opponents of the Dodo Bird Verdict have published numerous studies attempting to show that one type of psychotherapy is superior to others.[5,6,7,8]  Common Factors advocates say these reports are usually biased by researcher allegiance to the therapy shown to be more effective.[9] Investigators without evident biases, however,  have also reported differences in effectiveness between types of psychotherapy.[10] The argument still remains unresolved.[11,12] My own experience as a psychiatrist has suggested that both non-specific and specific factors play important roles in treating depression.


What about antidepressants? Does it matter which ones are prescribed or are they equally effective based on common biological and psychological factors?  Until recently, the belief in non-specific factors has prevailed with generalizations like:

(1)   “The effectiveness of antidepressant medications is generally comparable between classes and within classes of medications.”[13]

(2)  “Antidepressant effectiveness is influenced by the therapeutic alliance” [14]

 (3)  “Antidepressant benefits are primarily psychological.”[15,16]

 On the other hand, a growing number of psychiatrists and neuroscientists have been identifying specific factors to individualize the prescribing of antidepressants.[17] Government-funded projects like the National Institute of Mental Health’s EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study[18] are providing opportunities to validate these approaches by seeking specific therapeutic targets.[19] The field of pharmacogenetics is generating much new interest in this area.[20]

 A Systematic Approach for Choosing Between Common and Specific Factors

 Figure 1

Figure 1







Most likely the truth lies somewhere in between. Figure 1 presents a schematic diagram of the relationship between specific and non-specific indications for types of psychotherapy and antidepressants as suggested by clinical experience and available data. Abraham Maslow’s Hierarchy of Needs offers a classic reference for aligning treatment types with sources of dysfunction.[21] The physiological needs at the foundation of the pyramid are associated with biological depressions, the social needs at the middle with situational depressions and the psychological needs towards the top with more deeply rooted intrapsychic issues.

Both CBT and psychodynamic therapies could be applied over much of the upper four levels, although common factors might account for many of their benefits except at the extremes. For example, CBT might have specific benefits in connection with the lower part of the pyramid where comorbid anxiety, obsessive-compulsive and panic disorders have been shown to benefit from specialized behavioral treatment techniques.[22] Psychodynamic psychotherapy, on the other hand, has evidenced specific advantages in dealing with the more complex psychological issues in the upper region. Medications are often unnecessary at this level. The newer generation antidepressants like the selective serotonin reuptake inhibitors (SSRIs), norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) might have usefulness everywhere except at the extremes because of increased tolerability and specific benefits such as activation and calming. Finally, the potency and lower cost of the older multi-mechanism tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) might confer advantages at the base of the pyramid, where other psychotropics such as atypical neuroleptics and mood stabilizers may be required as well. New discoveries in neuroscience may some day point the way to pharmacological agents with specific effects that enable treatments for mood disorders to be personalized in more optimal ways.

There are many reasons why the Dodo Bird Verdict may not be entirely true. As indicated above, the specific circumstances of every individual depressed patient require an inordinately complex series of responses, sometimes psychotherapeutic, sometimes psychopharmacological and often both. Within each of those realms the relationship between patient and professional is a dynamic field with each signaling the other in myriad ways that determine therapeutic actions. The need to respond with appropriate words, emotions and behaviors is a reality that professionals know can make the difference between success and failure in relieving depression and saving lives. 

If all psychotherapies are sometimes effective in this endeavor, it may be because experienced therapists often use their "common factors" to rise above manualized protocols and favored theories at the critical moments separating good therapy from bad.[23] In the same way, knowledgable prescribers of antidepressants listen to their patients and select antidepressants with benefits and side-effect profiles most likely to meet patients’ needs. These careful processes of tracking human beings and applying pharmacological and psychotherapeutic skills in complex and dynamic ways have thus far been nearly impossible to test in any objective, reproducible way. To the extent that research studies do identify independent and dependent variables that capture these multi-faceted interactions, they are still often overly reductionistic. To measure the effect of any treatment or response has required the scaling of complex human events into formulas that computers can parse. Still, the effort to study and determine as objectively as possible what works best for depressed patients must continue with all possible energy and ingenuity.

The Dodo Bird reached its verdict in Alice in Wonderland because the "caucus-race" that it had initiated had no clear guidelines for determining success or failure. As long as the race away from depression is similarly uncertain, distinguishing the victors will be difficult. To those experiencing that race every day “up close and personal,” the winners are found to be those who are guided, encouraged and nourished across the finish line in every way humanly and chemically possible. The more tools we have to target and measure that process effectively, the more real winners there will be. Jerry Frank could have been discussing both pharmacological and verbal treatments when he spoke these words to the Association for the Advancement of Psychotherapy in New York on November 1, 1970:A major task...would be to learn to categorize patients in such a way as to be able to select the most appropriate method of therapy for them. One reason for the slowness of progress toward this goal may be that it is premature....Only as this knowledge is gained may we be able to sort out the specific contributions of different techniques from effects common to them all.[24]


1.Frank JD (1961) Persuasion and Healing. Baltimore, Johns Hopkins University Press.

 2. Carroll, L (1865) Alice’s Adventures in Wonderland. D. Appleton & Co., New York.

 3. Luborsky L, Rosenthal R, Diguer L, Andrusyna TP, Berman JS, Levitt JT, Seligman DA, Krause ED (2002) The dodo bird verdict is alive and well--mostly. Clinical Psychology-Science and Practice 9(1): 2-12.

 4. Frank JD (1972) Common features of psychotherapy, Aust. N.Z. J. Psychiatry 6:34-40. 

 5. Butler AC, Beck AT (1995) Cognitive therapy for depression.  48(3): 3-5.

 6. Leichsenring F, Leibing E (2003) The effectiveness of psychodynamic therapy and cognitive behavioral therapy in the treatment of personality disorders: a meta-analysis.Am J Psychiatry 160(7): 1223-32.

 7. Tolin DF (2010) Is cognitive-behavioral therapy more effective than other therapies? A meta-analytic review. Clin Psychol Rev 30(6):710-20.

 8. Gerber AJ, Kocsis JH, Milrod BL, Roose SP, Barber JP, Thase ME, Perkins P, Leon AC (2011) A quality-based review of randomized controlled trials of psychodynamic psychotherapy. Am J Psychiatry 168(1): 19-28.

 9. Munder T, Brütsch O, Leonhart R, Gerger H,  Barth J (2013) Researcher allegiance in psyhotherapy outcome research:An overview of reviews. Clinical Psychology Review 33(4): 501-11.

 10. Watske B, Rüddel H, Jürgensen R, Koch U, Kriston L, Grothgar B, Schultz H (2012) Longer term outcome of cognitive-behavioural and psychodynamic psychotherapy in routine mental health care: randomised control trial. Behav Res Ther 50(9): 580-7.

 11. Tsacher W, Junghan UM, Pfammatter M (2014) Towards a taxonomy of common factors in psychotherapy-results expert survey. Clin Psychol Psychother 21(1): 82-96.

 12. Gee, A (2011) Couch wars: Does one form of psychotherapy work better than another? Slate.com http://www.slate.com/articles/health_and_science/medical_examiner/2011/06/couch_wars.html

 13. American Psychiatric Association (2010) Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition, APA Press, Washington, D.C.

 14. Krupnick JL, Sotsky SM, Simmens S, Moyer J, Elkin I, Watkins J, Pilkonis PA (1996) The role of the therapeutic alliance in psychotherapy and pharmacotherapy outcome: findings in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. J Consult Clin Psychol 64(3): 532-9.

 15. Coyne JC (2012) Irving Kirsch: Deja vu all over again. Psychology Today, published March 8, 2012.

 16. Kramer PD, (2011) In defense of antidepressants. New York Times, published July 9, 2011.

 17. Metzner RJ (2013) The impact of neurochemical mediators on antidepressant effectiveness. ACS Chem Neurosci 18, 4(9): 1245-8.

18. Trivedi M (2012) Introduction to EMBARC Study. EMBARC website

 19. Millan MJ (2006) Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacology & Therapeutics 110(2): 135-370

 20. Fabbri C Porcelli S Serretti A (2014) From pharmacogenetics to pharmacogenomics: the way toward the personalization of antidepressant treatment. Can J Psychiatry 59(2):62-75.

 21. Maslow (1943) A theory of human motivation. Psychological Review 50, 370-396.

 22. Redei EE Andrus BM Kwasny MJ Seok J Cai X Ho J Mohr DC (2014) Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy Translational Psychiatry 4, e442; doi:10.1038/tp.2014.66

 23. Fiedler FE (1950) The concept of an ideal therapeutic relationship. Journal of Consulting Psychology 14(4): 239-245.

 24. Frank JD (1972) Common features of psychotherapy.  Aust. N.Z. J. Psychiatry 6:34-40.