Although multiple interventions exist for major depressive disorder (MDD), only partial response is achieved in many patients and recurrence is common. Combining medication and psychotherapy may enable more effective treatment of MDD.
TABLE. Patients with these clinical factors are likely to benefit from combined treatment
Although multiple interventions exist for major depressive disorder (MDD), only partial response is achieved in many patients and recurrence is common. With monotherapy approximately two-thirds of patients with MDD show a clinical response, but only about one-third achieve remission. Combination therapy has generally been found to be superior compared with single treatment although not all patients require combination therapy (Table).
There are several reasons that combining medication and psychotherapy may enable more effective treatment of MDD.1,2 Given variable response to treatments, combining a medication with psychotherapy increases the likelihood of response to at least one of them. In addition, the additive effects of combined treatment may better address ongoing vulnerability to depression, as found with recurrent depressive episodes, and persistent, adverse residual symptoms.
The treatments can work synergistically: Medication can increase the effectiveness of psychotherapy (eg, through easing problems with concentration and motivation), and psychotherapy provides a means to address adherence problems with medication. Moreover, combined treatment may enable lower medication doses thus having fewer adverse effects; and medication may reduce the need for persistent or more intensive psychotherapy by easing symptoms.
Not all patients require combination therapy to achieve symptom remission or prevent recurrence. Therefore, combination treatments may expose some patients to more treatment than is necessary. Questions of cost effectiveness arise with the greater expense of psychotherapy plus medication, although potential long-term benefits may outweigh the costs.
Another option is to sequence treatments for depression. Begin treatment with pharmacotherapy or psychotherapy, and if the patient does not have an adequate response, add psychotherapy or pharmacotherapy.3 Studies suggest that a switch to or addition of psychotherapy may decrease the risk of depression recurrence.4-6
Determing when to employ combined treatment strategies
Research findings suggest that chronic depression is more responsive to psychotherapy and medication, although dysthymia without accompanying MDD showed no additional value for combined treatment compared with medication alone.7,8 Psychotherapy may be an essential element in the treatment of depressed patients with a history of childhood trauma as well as those with comorbid personality disorder.9,10 In addition to comorbid personality disorder, combination therapy should be considered with other psychiatric comorbidities that are unlikely to respond fully to monotherapy, such as obsessive compulsive disorder, eating disorders, and posttraumatic stress disorder. Clinicians should also consider combined treatment if the patient experiences a high level of suffering and functional impairment and is at risk for suicide.
These recommendations are consistent with the American Psychiatric Association Practice guideline for the treatment of patients with MDD.
Combining a depression-focused psychotherapy and pharmacotherapy may be a useful initial treatment choice for patients with moderate to severe major depressive disorder. Other indications for combined treatment include chronic forms of depression, psychosocial issues, intrapsychic conflict, interpersonal problems, or a co-occurring Axis II disorder. In addition, patients who have had a history of only partial response to adequate trials of single treatment modalities may benefit from combined treatment. Poor adherence with pharmacotherapy may also warrant combined treatment with medications and psychotherapy focused on treatment adherence.11
Discussing the use of combined treatment with patients
The benefits and risks of the various interventions need to be discussed so that patients can be involved in treatment decisions. In explaining the combination of treatments, a metaphor of a river and depression may be helpful.12 The river is viewed as having psychological and/or emotional, biochemical, and environmental tributaries. The river overflowing its banks is seen as equivalent to a depressive disorder. Medication can have an impact on the biochemical contribution, whereas psychotherapy affects the psychological and emotional contributions. The psychiatrist could also explain that the various river tributaries are interconnected; therefore, psychotherapy also has a biochemical impact and medication modulates emotional and psychological factors.
In addition to the river analogy, similarities to treatment with other medical problems can be useful to explain the need for combined treatment. Combining medication and psychotherapy for depression can be compared with combining surgery and physical therapy for orthopedic problems. Similarly, an analogy can be made for combining medication, exercise, and nutritional interventions for diabetes. This perspective emphasizes that, for depression, as with many health conditions, it should not be an either/or between medications and non-medication treatments. This helps to clarify how medication and other forms of intervention can work together to produce a better outcome.
Many factors contribute to patient’s preferences regarding combining medication and psychotherapy, including family, cultural, and personality factors, as well as health belief models. Being able to acknowledge preferences in a nonjudgmental way while providing the rationale for recommending combined treatment, when appropriate, is an important component of dialogue.
Thomas M. Gutheil, MD,13 professor of psychiatry at Harvard, emphasized the concept of “participant prescribing,” in which the clinician collaborates with the patient in considering the potential impact, concerns, and problems with medication in the context of psychotherapy. Such an approach helps to avert potential power struggles involving the physician as the authority pressuring patients to comply with certain treatment, and patients resisting these efforts. An empathic exploration of the patients’ concerns about various treatment interventions will aid with compliance and provide information about psychological factors that may be relevant to symptoms and other life problems.
Considering psychological vulnerabilities to depression
Knowledge of psychological vulnerabilities to depression can aid in addressing problems that can occur in accepting combined treatment. Patients can struggle with low self-esteem, shame, and narcissistic sensitivity that precede or are exacerbated by depression onset. At risk individuals are sensitive to disappointment and rejection, responding with a sense of injury and anger. This anger is often conflicted, triggering feelings of guilt and worthlessness, and it can become directed inward in the form of self-critical thoughts and feelings. Another core dynamic in depression is the patient’s attempt to deal with low self-esteem by a compensatory idealization of self or others. However, this idealization increases the likelihood and intensity of eventual disappointments, worsening depression.
Patients can experience shame about their depression, and the illness itself tends to exacerbate self-critical tendencies and feelings of being a bad person. Patients may therefore resist treatments if they experience these interventions as further indications that they are indeed defective, as another narcissistic injury. Thus, they may use medication as a resistance to psychotherapy, if they see the need for therapy as shameful, or they may resist medication if they view this need as a source of shame.
Furthermore, patients may idealize one or the other treatment as the answer to depression. Such idealization can lead to significant disappointment when the patient realizes that other problems persist or there is a recurrence of depression. Addressing patient resistance can be valuable, particularly when patients are best served by combination treatment.
“Angela,” a 25-year-old real estate agent, whose depression responded to treatment with sertraline and psychodynamic psychotherapy, experienced a recurrence of depression. She admitted that she had not been taking the medication consistently and the recurrence happened not long after. Further questioning revealed that angela viewed medication as a narcissistic injury, a sign that she was defective in some way.
Her negative feelings about taking antidepressants contributed to her sense of isolation and jealousy, which she often experienced when growing up. During that time she had viewed herself as less wealthy and not as cool as others in her community. She felt her father was uninterested in her and withdrawn, which she ascribed to her being unappealing and unattractive.
Her feelings of inadequacy and defectiveness had recently intensified in the context of difficulties with her career including a lack of sales. These problems with her job and associated painful feelings of inadequacy appeared to trigger resurgences of depressive symptoms.
Early life and current stresses, along with negative self-appraisals, seemed to trigger a biochemically based depression, which exacerbated her feelings of inadequacy, low self-esteem and jealousy. Medication played an important role in helping to relieve this cycle.
Her therapist found it essential to explore her difficulties in complying with treatment with antidepressants and explained that noncompliance was exacerbating her problems. When the therapist asked more about her feelings of being defective, Angela stated it meant something was wrong with her and people would not want to be with her.
The therapist suggested that it was important to understand how the medication became connected to negative self-views, as discontinuing it exacerbated her depressive symptoms. Angela responded that she had previously not connected her discontinuing medication with hurt and anger at her father and would remind herself of this link when she felt an urge to stop taking it. If she became aware of forgetting doses, she would raise it with the therapist for further exploration.
Psychotherapy as an aid to medication adherence
Many variables contribute to medication nonadherence, including poor psychoeducation and limited monitoring as well as cultural, psychological, and emotional factors. Shame about depression, medication, or psychotherapy can lead to disruptions in treatment. Adverse effects that are unaddressed can also play a role. Psychotherapy provides an opportunity to explore how patients are affected by various adverse effects and what changes may be necessary in treatment regimens. In addition, common adverse effects may be experienced differently by patients based on their psychological vulnerabilities. For instance, sexual adverse effects could be experienced as an attempt to undermine the patient’s power or as a punishment.
Some patients struggle with recurrent negative reactions to medication-the nocebo effect-that go beyond or are not consistent with possible adverse effects. The nocebo effect can lead to recurrent discontinuation of medications and add to a negative view of the clinician. A history of trauma can contribute to a recurrent nocebo effect, as patients may perceive the medication as an unwelcome intrusion or the doctor prescribing medication as a potential abuser. Psychotherapeutic interventions can be used to address negative reactions to medication and a possible negative transference reaction to the clinician.
The psychotherapist as prescriber vs psychotherapy/pharmacotherapy triangles
Combined therapy requires either a therapist who is also a prescriber or split treatment in which a therapist provides psychotherapy and a psychiatrist (or other physician) prescribes medication. A psychiatrist who provides both treatments has the advantage of avoiding conflicts between two treating clinicians. Similarly, more frequent visits allow the psychiatrist further opportunities to monitor the effects of medications. However, a psychiatrist who provides psychotherapy may not consistently assess symptoms and medication effects that are central to psychopharmacological visits. This puts the patient at risk of the covert development of a disorder not detected by the treating psychiatrist. It is of value for psychotherapists prescribing medication to arrange some system for regular monitoring of symptoms and medication.
In split treatment, competitive and professional tensions between the two practitioners, as well as different theoretical and clinical models, can generate problems in treatment management. Patients may idealize and devalue one or the other of the clinicians or treatments, or act out in ways that may be difficult to address (such as suddenly stopping medication). Maintaining a triadic therapeutic alliance between the therapist, psychopharmacologist, and patient as well as communication between the treating clinicians can help identify and address problem areas.14
Dr Busch is Clinical Professor of Psychiatry, Weill Cornell Medical College, New York, NY. He is coauthor of Psychotherapy and Medication: The Challenge of Integration with Larry S. Sandberg and Psychodynamic Treatment of Depression, second edition with Marie Rudden and Theodore Shapiro. He receives royalties from the books; otherwise he has no conflicts of interest concerning the subject matter of this article.
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