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Does psychotherapy share common neuronal pathways with psychopharmacology

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.

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