Treatment of Major Depression


The first and most critical decision the therapist must make is whether to hospitalize a patient with major depression, or to attempt outpatient treatment. Clear indications for hospitalization are: (1) risk of suicide or homicide, (2) grossly reduced ability to care for food, shelter, and clothing, and (3) the need for medical diagnostic procedures. A patient with mild to moderate depression may be safely treated in the office if the therapist evaluates the patient frequently. The patient’s support system should be strengthened and involved in treatment whenever possible.


Studies have show that antidepressant therapy for major depression can dramatically reduce suicide rates and hospitalization rates. Unfortunately, very few suicide victims receive antidepressants in adequate doses, and - even worse - most receive no treatment for depression whatsoever.

One of the biggest problems with antidepressant therapy is that most patients don’t stay on their antidepressant medication long enough for it to be effective. A recent study found that only 25% of patients started on antidepressants by their family physician stayed on it longer than one month. Antidepressant therapy usually takes 2-4 weeks before any significant improvement appears (and 2-6 months before maximal improvement appears).
First Line Antidepressants

The SSRI antidepressants, escitalopram (Lexapro), Fluoxetine (Prozac), paroxetine (Paxil), fluvoxamine (Luvox), or sertraline (Zoloft), are considered excellent choices as the patient’s first antidepressant because of their low incidence of side-effects (especially weight gain) and their low lethality if taken in an overdose. All SSRI antidepressants are equally effective.

Because many patients with major depression also suffer with intense anxiety, your doctor may also give you Fluvoxamine (Luvox) or lorazepam (Ativan) to reduce anxiety in mixed anxiety-depression.

Both Fluoxetine (Prozac) and paroxetine (Paxil) tend to be stimulating (elevate your mood); thus patients with mixed anxiety-depression can often dramatically benefit from the addition of clonazepam (Klonopin) to the Fluoxetine (Prozac) or paroxetine (Paxil) therapy.

Keep in mind, prescribing the right antidepressant is not an exact science. It may take some experimentation on the part of the doctor (make sure you’re seeing a psychiatrist, a specialist in psychiatric medications) to find the right antidepressant and right dosage for you. Do not give up if everything doesn’t come together right away.

SSRI antidepressants should be taken for 6 to 12 months. Antidepressant therapy should not be withdrawn before there have been 4 to 5 symptom-free months. Withdrawal from antidepressant therapy should be gradual. Never discontinue taking your medication without telling your doctor first. Suddenly stopping your medication could produce severe withdrawl symptoms and unwanted psychological effects, including a return of major depression.


In general, psychiatrists agree that severely depressed patients do best with a combination of antidepressant medications and psychotherapy. Medications relieve the symptoms of depression quickly, while psychotherapy can help the patient deal with the illness, easing some of the potential stresses that can trigger or exacerbate the illness.
Dynamic Psychotherapy

Dynamic Psychotherapy is based on the premise that human behavior is determined by one’s past experience (particularly in childhood), genetic endowment and current life events. It recognizes the significant effects of emotions, unconscious conflicts and drives on human behavior.
Interpersonal Therapy

Interpersonal Therapy is based on the theory that disturbed social and personal relationships can cause or precipitate depression. The illness, in turn, may make these relationships more problematic. IPT helps the patient understand his or her illness and how depression and interpersonal issues are related.

There is some evidence in controlled studies that IPT as a single agent is effective in reducing symptoms in acutely depressed patients of mild to moderate severity.

The National Institute of Mental Health studied interpersonal therapy as one of the most promising types of psychotherapy. Interpersonal therapy (IPT) is a short-term psychotherapy, normally consisting of 12 to 16 weekly sessions. It was developed specifically for the treatment of major depression, and focuses on correcting current social dysfunction. Unlike psychoanalytic psychotherapy, it does not address unconscious phenomena, such as defense mechanisms or internal conflicts. Instead, interpersonal therapy focuses primarily on the “here-and-now” factors that directly interfere with social relationships.
Behavior Therapy

Behavior therapy involves activity scheduling, self-control therapy, social skills training, and problem solving. Behavior therapy has been reported to be effective in the acute treatment of patients with mild to moderately severe depressions, especially when combined with pharmacotherapy.

Cognitive Behavior Therapy (CBT)

The cognitive approach to psychotherapy maintains that irrational beliefs and distorted attitudes toward the self, the environment and the future, perpetuate depressive affects and that these may be reversed through CBT.

There is some evidence that cognitive therapy reduces depressive symptoms during the acute phase of less severe forms of depression.

Electroconvulsive Therapy (ECT)

ECT is primarily used for severely depressed patients who have not responded to antidepressant medicines, and who frequently have psychotic features, acute suicidality, or food refusal. It can also be used for patients who are severely depressed and have other chronic general medical illnesses which make taking antipsychotic medications difficult. Changes in the way ECT is delivered have made ECT a better tolerated treatment.
Importance of Continuation of Treatment

There is a period of time following the relief of symptoms during which discontinuation of the treatment would likely result in relapse. The NIMH Depression Collaboration Research Program found that four months of treatment with medication or cognitive behavioral and interpersonal psychotherapy is insufficient for most depressed patients to fully recover and enjoy lasting remission. Their 18-month follow-up after a course of treatment found relapses of between 33 and 50 percent of those initially responding to a short-term treatment.

The current available data on continuation of treatment indicate that patients treated for a first episode of uncomplicated depression who exhibit a satisfactory response to an antidepressant should continue to receive a full therapeutic dose of that medication for at least 6-12 months after achieving full remission. The first eight weeks after symptom resolution is a period of particularly high vulnerability to relapse. Patients with recurrent depression, dysthymia or other complicating features may require a more extended course of treatment.

In a 1998 article, in the Harvard Review of Psychiatry, entitled “Discontinuing Antidepressant Treatment in Major Depression, the authors concluded:

  “The benefits of long-term antidepressant treatment in major depression and the risks of discontinuing medication at various times after clinical recovery from acute depression are not as well defined. Computerized searching found 27 studies with data on depression risk over time including a total of 3037 depressive patients treated for 5.78 (0-48) months and then followed for 16.6 (5-66) months with antidepressants continued or discontinued. Compared with patients whose antidepressants were discontinued, those with continued treatment showed much lower relapse rates (1.85 vs. 6.24%/month), longer time to 50% relapse (48.0 vs. 14.2 months), and lower 12-month relapse risk (19.5 vs. 44.8%) (all p

< 0.001). However, longer prior treatment did not yield lower postdiscontinuation relapse risk, and differences in relapses off versus on antidepressants fell markedly with longer follow-up. Contrary to prediction, gradual discontinuation (dose-tapering or use of long-acting agents) did not yield lower relapse rates. Relapse risk was not associated with diagnostic criteria. More previous illness (particularly three or more prior episodes or a chronic course) was strongly associated with higher relapse risk after discontinuation of antidepressants but had no effect on response to continued treatment; patients with infrequent prior illness showed only minor relapse differences between drug and placebo treatment.

Refractory Depression

Refractory depression occurs in as many as 10 to 30 percent of depressive episodes, affecting nearly a million patients. Katherine A. Phillips, M.D. (a 1992 NARSAD Young Investigator) has found that failure to provide adequate doses of medication for sufficient periods of time is perhaps the most common cause of apparent treatment resistance. Once the clinician has determined that a patient is truly treatment-refractory, many treatment approaches can be tried. Phillips recommends the following treatment strategies for refractory depression:

  1. Augmentation with lithium, and perhaps other agents like liothyronine (T3 or L-triiodothyronine) (Cytomel). Trazodone may be worth trying either alone or in combination with Fluoxetine or tricyclics if other approaches have failed.  
  2. Combining antidepressants - supplementing the SSRI antidepressant with a tricyclic antidepressant. Several studies have shown a good response when Fluoxetine is added to tricyclics and when tricyclics are added to Fluoxetine. It is important to monitor tricyclic levels because Fluoxetine can raise tricyclic levels by 4- to 11- fold and thereby cause tricyclic toxicity.  
  3. Switching antidepressants - stop the first SSRI antidepressant gradually (over one week), then substitute another SSRI antidepressant or SNRI antidepressant (Effexor). Fluvoxamine (Luvox), sertraline (Zoloft), or venlafaxine (Effexor) often are effective for Fluoxetine or paroxetine nonresponders (and visa versa).


Provided by ArmMed Media
Revision date: June 22, 2011
Last revised: by Amalia K. Gagarina, M.S., R.D.