Combining Drug Therapy and Psychotherapy for Depression (2023)

It was just over a generation ago that the routine combination of psychotherapy and drug therapy seemed impossible. Especially in America, psychiatry was polarized by ideologic and political struggles between psychoanalysis and biologic psychiatry. American psychoanalysts tended to regard psychopharmacology as an inferior treatment that covered over problems rather than addressing them. They assumed that symptoms suppressed by drugs would eventually be replaced by others equally disabling. In turn, proponents of biologic psychiatry often viewed psychoanalysis as a form of quackery that was, at best, a costly waste of time, and, at worst, heightened distress that the psychopharmacologist was trying to ameliorate.

Benefits of combined treatment

In the 1970s, a number of influential studies cut through ideologic assumptions and began to reshape the way we viewed the practice of combining therapy and medications. Klerman and coworkers1 tested the assumption that psychotherapy and psychopharmacology were essentially in conflict, each undermining the work of the other. There was no evidence that psychopharmacologic treatment led to therapy discontinuation or to symptom substitution or that psychotherapy exacerbated patients' distress. Then, Luborsky and colleagues,2 in a meta-analysis comparing the effectiveness of different psychodynamic psychotherapies, made an interesting discovery. All therapies were equally effective, with one notable exception: combined treatment with psychotherapy and medication was found to be notably superior to either treatment alone.

Since then, numerous studies have shown combined treatment for depression to have many benefits over single-modality treatment (Table 1). This applies not only to psychodynamic therapy, but also to interpersonal therapy (IPT), a manualized descendent of psychodynamic psychotherapy.3 The evidence was less clear for cognitive-behavioral therapies (CBT), with several early studies showing only nonsignificant trends toward a benefit of combined treat- ment.4 It appears, however, that this may reflect limitations in study design typical of that period.5 Other studies showed a benefit to combining CBT and pharmacotherapy.6-8

TABLE 1Empirically validated benefits of combined treatment
FindingSupporting evidence
Improved short-term recovery ratesMultiple studies
Faster responsesBowers, 1990
Improved long-term recovery ratesFava et al, 1998
Decreased rate of relapsePaykel et al, 1999
Improved long-term social functioningKlerman et al, 1974
Improved medication complianceBasco and Rush, 1995
Greater patient satisfactionSeligman, 1995
Lower long-term health and social service costsBrowne et al, 2002

Does this mean that all patients presenting with depression should be offered treatment with a combination of psychotherapy and medications? In an ideal world with unlimited resources, this might be the case. However, there is the cost/benefit ratio to consider. Though combined treatment is more effective than single-modality treatment, the effect sizes are generally modest.9 Differences that are statistically significant may not be clinically significant. Given the added strain of providing combined treatment on limited mental health services, it would be far better selectively to provide combined treatment to those patients most likely to show a significant benefit.

Types of patients likely to respond to combined treatment

Although the evidence base is still rather small, there is some guidance about which patients with depression would most likely have a substantial benefit from combined treatment. Patients with more severe depression,10 endogenous depression,11 chronic depression,12-14 and dysfunctional cognitions15 all show more robust and clinically significant responses to combined treatment (Table 2).

TABLE 2Patients demonstrating aclinically significant responseto combined treatments
Patients with severe depressionBowers, 1990
Patients with endogenous (nonsituational) depressionPrusoff et al, 1980
Patients with chronic depressionKeller et al, 200014;Hellerstein et al, 2001
Patients with dysfunctional cognitionsMiller et al, 1990
Incomplete responders topharmacotherapy aloneFava et al, 1994
Incomplete responders to psychotherapy aloneThase et al, 1997

Inadequate response to single-modality treatment is another reason to consider combined treatment. Patients whose depression has not responded well to antidepressant therapy alone show an increased rate of response when that treatment is paired with psychotherapy.16 Similarly, nonresponders to psychotherapy receive added benefit when antidepressants are added.17 It is worth noting that these categories of patients are the ones that typically are receiving treatment from psychiatrists. With the majority of antidepressants prescribed by nonpsychiatrists, psychiatrists typically see patients with more severe, chronic, and treatment-resistant conditions and those patients whose treatments are complicated by dysfunctional attitudes and maladaptive personality styles. Consequently, most patients receiving referral for specialized psychiatric treatment would be appropriately treated with combined treatment with psychotherapy and medications.

Combined treatment produces not only faster8 and greater short-term benefits, but greater long-term benefits as well. Patients receiving combined treatment with CBT have a lower relapse rate than do patients receiving medications alone.18,19 Patients who received IPT and drugs had better long-term social adjustment than patients on drugs alone.1 For patients older than 60 years, the combination of IPT and medication has been shown to reduce the rate of depressive relapse.20 In addition, compared with pharmacotherapy alone, combined medication and group therapy seems to reduce relapse after discontinuation of treatment.13

What makes combined treatment better?

We still do not know much about what accounts for the superiority of combined treatment.Some benefit may accrue simply from additive effects.Each treatment is effective in its own right; thus, adding the effectiveness of each provides a cumulative effect.Additive effects may result from the fact that therapy and medications converge on the problem of depression from 2 different angles, perhaps even literally.Functional neuroimaging of the differential effects of psychotherapy and antidepressant medications suggests that, while both treatments show considerable overlap in effects on cerebral metabolism, medication effects develop "bottom up," emanating from the brain stem upward, while psychotherapy effects emerge in a "top down" fashion, spreading downward from the frontal cortex.21 The 2 modalities may exert an additive effect by addressing different symptom domains. Therapy, for example, might address the hopelessness related to depres- sion, while medications more directly address neurovegetative aspects of depression.22

There may also be interactive effects that contribute to the increased efficacy of combined treatment. Pharmacotherapy may, for example, make some patients more available for therapy by easing treatment-interfering problems such as psychosis, disabling anxiety, or the amotivational syndrome of depression. Recent evidence suggests that there may also be some more directly biologic interactive effects. One of the neurobiologic effects of antidepressant use appears to be an increase in neural turnover, with increased sprouting and trimming of dendritic synapses.23 This intriguing research suggests that antidepressants may make for more plastic neural networks, which may, in turn, allow for more rapid learning, as in psychotherapy.

Psychotherapy may also enhance the effectiveness of medication. One way in which this may occur is through improved compliance. Several studies have demonstrated that patients receiving psychotherapy concurrently with medications have a lower rate of pharmacologic treatment discontinua- tion.23-26 Concurrent treatment may also improve the therapeutic alliance27 and enhance patient satisfaction with treatment.25,28 The therapeutic alliance, in turn, has a profound effect on antidepressant efficacy.29 Additionally, the psychosomatically preoccupied patient prone to negative medication reac- tions may benefit from attention to psychological origins of somatic reactions.27,30

Combining and integrating treatments

How does one go about combining treatments? Some of the more robust findings in favor of combined treatment have been associated with structured and highly integrated forms of care, such as IPT or the cognitive behavioral analysis system of psychotherapy (CBASP). It seems likely that treatment integration is related to outcome. A treatment in which the psychopharmacologist and psychotherapist are openly skeptical of each other's work and are working at cross-purposes is not likely to be successful.

When there is a split treatment arrangement, with one person providing psychotherapy and another providing psychopharmacology, good communication between treaters and the sharing of overall treatment goals may enhance treatment. Treatments in which the pharmacologic work is seen to support the therapy and the therapy supports the drug treatment may be the most integrated, as with the model of psychodynamic psychopharmacology developed by Mintz and Belnap,27 which is tailored for work with treatment-resistant patients. In this model, pharmacologic treatment is aimed primarily at supporting the capacity of the patient to usefully engage in psychotherapy. The therapist then feels a direct connection to the medications and sees problems with medication (eg, noncompliance, fear of dependency, a tendency to develop side effects) as targets for therapeutic exploration. The psychotherapy then explicitly supports the patient's healthy use of medication. The same kind of integrative approach could be undertaken with CBT and medication.

It is not clear at this point whether a single-provider model enhances treatment integration and outcome. To date, there are no published studies that address this issue. In the absence of evidence that single-provider treatments are superior, the economics of health care have tended to promote the delivery of split treatments under the assumption that it would be less costly to have psychotherapy provided by a lower-paid, nonmedical therapist than by the prescribing psychiatrist.

In contrast to this assumption, 2 studies using different methodologies, have examined the question of which treatment (single-provider or split) was more costly.31,32 Both studies found single-provider combined treatment to be less costly than split treatments with a psychiatrist/pharmacologist and a nonmedical therapist. While it is not yet clear whether single-provider treatment is more clinically effective than split treatment, the evidence suggests that it is more cost-effective.

While combined treatment has been shown to be generally more effective than single-modality treatments and substantially more effective for certain kinds of patients, there is still much work that needs to be done to establish whether there are other subpopulations of patients with depression who would benefit from combined treatment. There is also still much to learn about the specific factors (eg, treatment integration) that contribute to the greater treatment effectiveness of combined treatment.

Dr Mintz is director of residency training and continuing medical education at the Austen Riggs Center in Stockbridge, Mass. He reports no conflicts of interest concerning the subject matter of this article.




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DiMascio A, Weissman MM, Prusoff BA, et al. Differential symptom reduction by drugs and psychotherapy in acute depression.

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Thase ME, Buysse DJ, Frank E, et al. Which depressed patients will respond to interpersonal psychotherapy? The role of abnormal EEG sleep profiles.

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Prusoff BA, Weissman MM, Klerman GL, Rounsaville BJ. Research diagnostic criteria subtypes of depression: their role as predictors of differential responses to psychotherapy and drug treatment.

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Hellerstein DJ, Little SA, Samstag LW, et al. Adding group psychotherapy to medication treatment in dysthymias: a randomized prospective pilot study.

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Keller MB, McCullough JP, Klein DN, et al. A comparison of nefazedone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression.

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Thase ME, Greenhouse JB, Frank E, et al. Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy combinations.

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Fava GA, Grandi S, Zielesny M, et al. Cognitive behavioral treatment of residual symptoms in primary major depressive disorder.

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Teasdale JD, Segal ZV, Williams JM, et al. Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy.

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(Video) Combinations for Treatment-Resistant Depression

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Goldapple K, Segal Z, Garson C, et al. Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy.

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Mayberg HS. Modulating limbic-cortical circuits in depression: targets of antidepressant treatments.

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Basco MR, Rush AJ. Compliance with pharmacotherapy in mood disorders.

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de Jonghe F, Kool S, van Aalst G, et al. Combining psychotherapy and antidepressants in the treatment of depression.

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(Video) NUR140 Chapter 07 Psychotherapeutic Drug Therapy


What is the ideal combination of treatment for someone with depression? ›

Medications and psychotherapy are effective for most people with depression. Your primary care doctor or psychiatrist can prescribe medications to relieve symptoms. However, many people with depression also benefit from seeing a psychiatrist, psychologist or other mental health professional.

What is an advantage of psychotherapy over antidepressant drugs? ›

In fact, not only is it more cost-effective, but psychotherapy leads to fewer relapses of anxiety and mild to moderate depression than medication use alone—so much so that Norwegian Health Authorities have issued new guidelines concerning treatment of mild to moderate depression and anxiety, stating that psychological ...

Which two therapies may be equally effective in reducing depression? ›

Two types of therapy have been shown to be most effective: Cognitive Behavioural Therapy (CBT) and Interpersonal Therapy (IPT).

Which form of therapy is most effective for major depression? ›

Cognitive behavioral therapy (CBT)

This type of psychotherapy focuses on changing both negative thought processes and behaviors that contribute to depression symptoms. According to research, CBT offers some of the most promising evidence for effective therapeutic treatment for depression available.

What is the gold standard treatment for depression? ›

Cognitive behavioral therapy (CBT)

Cognitive behavioral therapy is the gold standard therapy for treating children and adolescents with depression.

Do Pharmacotherapy and psychotherapy complement each other? ›

The two most powerful tools in the treatment of psychiatric disorders are psychopharmacology and psychotherapy. In most cases, patients greatly benefit from a combination of both; however, due to increasing specialisation, this is less and less provided by the same therapist.

Is it better to treat mental disorders with drugs or psychotherapy? ›

Research generally shows that psychotherapy is more effective than medications, and that adding medications does not significantly improve outcomes from psychotherapy alone.

What is the success rate of psychotherapy for depression? ›

To put this more clearly: If you are diagnosed with depression, you have a 24.2% chance of getting better (even after aggressive treatment, including multiple drugs and hospitalization). However, you're about twice as likely (41.4%) to be called “treatment-resistant” at the end of that treatment and see no improvement.

What are the negatives of psychotherapy? ›

Some negative effects were generally uncommon but commonly related to treatment, including dependency on the therapist, feeling ashamed because of the treatment, or demoralisation. Slightly fewer than one-fifth reported problems in understanding the treatment or the therapist.

Why would a combination of therapy and medication be the most beneficial treatment for depression? ›

One report that pooled findings from 25 studies found that adding psychotherapy to drug treatment was more helpful than medication alone in treating major depression. Earlier research suggested that one reason therapy and medication may complement each other is that they have different effects on the brain.

What is the first choice in drug treatment for depression? ›

SSRIs are usually the first choice medicine for depression because they generally have fewer side effects than most other types of antidepressant. As well as depression, SSRIs can be used to treat a number of other mental health conditions, including: generalised anxiety disorder (GAD)

What are the 3 basic approaches to treating depression? ›

Three of the more common methods used in depression treatment include cognitive behavioral therapy, interpersonal therapy, and psychodynamic therapy.

Which type of therapy is often used to treat depression? ›

Cognitive Behavioral Therapy (CBT)

Cognitive behavioral therapy, or CBT, helps an individual identify and change negative thoughts and associated behaviors. People who suffer from depression often struggle with negative thought patterns.

How many sessions are required for depression? ›

Having more than eight sessions does not confer any additional benefit. Indeed, there is little difference between 1-5 sessions and more than eight sessions for depression.

What are the 2 types of treatment for major depressive disorder? ›

Cognitive behavioral therapy (CBT): CBT helps you identify and change negative thinking and behavioral patterns that can affect how you feel. Interpersonal therapy (IPT): IPT is another form of therapy for depression that focuses on improving your relationships with other people.

What is second line treatment for depression? ›

Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors are considered second line due to tolerability and safety issues. Other adjunctive medications include atypical antipsychotics, lithium, adding a second antidepressant, buspirone, and thyroid hormone (T3) among others.

What is the most effective psychotherapy? ›

The most robustly studied, best-understood, and most-used is cognitive behavioral therapy. Other effective therapies include light therapy, hypnosis, and mindfulness-based treatments, among others.

What is the absolute best antidepressant? ›

Bupropion and mirtazapine are as effective as SSRIs and SNRIs. And both are considered first-choice options for treating depression. But trazodone may be a better choice if a person has both depression and insomnia (trouble sleeping).

What drug enhances psychotherapy? ›

LSD was thus the prototypical substance in the development of radically new forms of psychotherapy, including psychedelic-assisted psychotherapy (Pahnke et al., 1970; Grof, 1971, 2008) and another approach based on repeated low doses (10 to 50 μg) to potentiate psychoanalysis, known as psycholytic psychoherapy (Majić ...

Which form of therapy is most easily combined with medication management? ›

CBT is the most well-studied form of psychotherapy for depression and has been shown to be effective when used alone or in combination with medication. Patients receiving CBT work collaboratively with their therapists to learn specific skills to solve their problems and manage their emotions.

What are the four major approaches to psychotherapy integration? ›

Integration in psychotherapy involves four possible approaches: theoretical integration (i.e., transcending diverse models by creating single but different approach), technical eclecticism (i.e., using effective ingredients from different approaches), assimilative integration (i.e., working primarily from within one ...

Can a psychotherapist recommend medication? ›

California psychologists cannot legally prescribe medication. This prohibition is established in Section 2904 of the California Business and Professions Code.

What are 3 therapy methods for treating mental disorders? ›

Treatment of Mental Illness
  • Drug Therapy.
  • Psychotherapy.
  • Electroconvulsive Therapy.

What is the difference between drug therapy and psychotherapy? ›

Unlike with the potential of some psychotropic medications, psychotherapy is not addictive. Furthermore, some studies have shown that Cognitive Behavioral Therapy can be more effective at relieving anxiety and depression than medication.

How long does it take to see results from psychotherapy? ›

The number of recommended sessions varies by condition and treatment type, however, the majority of psychotherapy clients report feeling better after 3 months; those with depression and anxiety experience significant improvement after short and longer time frames, 1-2 months & 3-4.

How long does it take for psychotherapy to work? ›

So how long does it typically take for treatment to work? Recent research indicates that on average 15 to 20 sessions are required for 50 percent of patients to recover as indicated by self-reported symptom measures.

What is the new treatment for depression? ›

Currently, esketamine is approved for people with treatment-resistant depression. That means you've tried at least two other antidepressants (for at least six weeks each) and haven't experienced remission or at least a 50% improvement in mood.

When should you stop psychotherapy? ›

There is no “right” length of time to be in therapy. But for most people, there will come a time when therapy no longer feels necessary or progress has stalled. In most cases, the client will choose to end therapy; there are also situations in which a therapist decides to end sessions and refer a client elsewhere.

What is the failure rate of psychotherapy? ›

In psychotherapy we are also aware of the important fact that the amount of unwanted effects is very similar to fields such as pharmacotherapy, and the number of patients reporting unwanted effects of psychotherapy is between 3 and 15% of cases (Berk and Parker, 2009).

What conditions are best treated with psychotherapy? ›

Psychotherapy can be helpful in treating most mental health problems, including: Anxiety disorders, such as obsessive-compulsive disorder (OCD), phobias, panic disorder or post-traumatic stress disorder (PTSD) Mood disorders, such as depression or bipolar disorder.

What is superior to other treatment options used to treat patients with depression? ›

Electroconvulsive therapy can work for severe depression that doesn't respond to other treatments. Also called electroshock therapy, it's the best proven option for such people.

What are the benefits of combining behavior treatment and medication? ›

There is an added benefit from combination treatment, says Kobylski, who is chairman of the Washington area chapter of the American Academy of Child and Adolescent Psychiatry. Studies have found that children treated with behavior therapy can take a lower dose of medication, Kobylski says.

Do antidepressants work with therapy? ›

A GP may recommend that you take a course of antidepressants plus talking therapy, particularly if your depression is quite severe. A combination of an antidepressant and CBT usually works better than having just one of these treatments.

What is the best initial treatment for a person with moderate to severe depression? ›

Antidepressant medication may be used as initial treatment modality for patients with mild, moderate, or severe major depressive disorder.

Which medications are best for treating depression in later life? ›

Selective serotonin reuptake inhibitors (SSRIs) are antidepressants commonly prescribed to older adults. A psychiatrist, mental health nurse practitioner, or primary care physician can prescribe and help monitor medications and potential side effects.

What therapy is most successful in treating depression? ›

Cognitive Behavior Therapy (CBT)

This form of therapy is considered by many to be the gold standard in depression treatment.

Which psychological approach is best for depression? ›

Cognitive behaviour therapy (CBT)

CBT is one of the most effective treatments for depression, and has been found to be useful for a wide range of ages, including children, adolescents, adults and older people.

What is the minimum time a depressive episode must last? ›

A depressive episode lasts at least two weeks, and the symptoms of depression are persistent and occur nearly every day for the duration of the episode. They cannot be explained by another medical condition or by substance abuse.

Is depression a lifelong condition? ›

Major depressive disorder isn't something that eventually “passes.” While most people feel sad at times in their lives, major depression is when a person is in a depressed mood most of the day, nearly every day, for at least two weeks.

How often does therapy work for depression? ›

Around 80 percent to 90 percent of people with depression respond well to some type of treatment, whether it be psychotherapy (talk therapy), medication, or a combo of both, according to the American Psychiatric Association. This makes it one of the most treatable mood disorders.

What are the 5 criteria for MDD? ›

DSM-5 Criteria for Major Depressive Disorder
  • Depressed mood. ...
  • Loss of interest/pleasure. ...
  • Weight loss or gain. ...
  • Insomnia or hypersomnia. ...
  • Psychomotor agitation or retardation. ...
  • Fatigue. ...
  • Feeling worthless or excessive/inappropriate guilt. ...
  • Decreased concentration.

What shrinks with major depressive disorder? ›

Shrinkage Of Several Brain Regions

One of the most common changes seen in a depressed patient's brain is shrinkage, especially in the hippocampus, thalamus, frontal cortex, and prefrontal cortex. How much these brain areas shrink depends on the length and severity of your depression.

What are the 3 main symptoms of depressive disorders? ›

  • Feelings of sadness, tearfulness, emptiness or hopelessness.
  • Angry outbursts, irritability or frustration, even over small matters.
  • Loss of interest or pleasure in most or all normal activities, such as sex, hobbies or sports.
  • Sleep disturbances, including insomnia or sleeping too much.
14 Oct 2022

What is the treatment of choice for patients with depressive personality? ›

Antidepressants. Antidepressants may be useful if you have a depressed mood, anger, impulsivity, irritability or hopelessness, which may be associated with personality disorders.

What treatments or combination of treatments are most effective? ›

Cognitive-behavioral therapy, interpersonal psychotherapy and antidepressant medications have all been shown to be helpful, and some evidence suggests that combining psychotherapy and medications may be more effective than either treatment alone.

What is the recommended way to treat depression by many therapists? ›

Two of the most common evidence-based therapies for depression are cognitive behavioral therapy and interpersonal therapy. Cognitive Behavioral Therapy (CBT) is a type of therapy in which patients learn to identify and manage negative thought and behavior patterns that can contribute to their depression.

What is the first line of treatment for major depression? ›

TREATMENT FOR MAJOR DEPRESSION — For the initial treatment of major depression, we suggest a combination of antidepressant medication and psychotherapy. Well-designed studies have shown that combination treatment is more effective than either treatment on its own.

What are some problems with drug combination therapy? ›

Cons: Some concerns about using fixed-dose combination drugs include the lack of flexibility in altering the dosing of individual components and the exposure of patients to unnecessary therapy.

Why is combination drug therapy used? ›

Combination therapy is the suggested way to increase treatment efficacy, to prevent the development of drug resistance, and to reduce the duration of treatment.

Can a psychotherapist prescribe medication? ›

Most psychotherapists cannot prescribe medication to their patients. Their job duties are to provide psychological treatment and therapy to mental health patients rather than medication.

What is the best treatment protocol for major depressive disorder? ›

Psychotherapy is usually recommended for patients with depression who are experiencing stressful life events, interpersonal conflicts, family conflicts, poor social support and comorbid personality issues.


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