Clinical depression medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The treatment of depression is highly individualized to the patient, based on the patient's unique combination of biological, psychological and social health factors and the severity of their condition. The three most conventional treatments for depression include medication, psychotherapy, and Electroconvulsive therapy, however new treatments and less conventional options are also available, including self help, life style changes, and vagus nerve stimulation. If there is an imminent threat of suicide or the patient is a danger to others, hospitalization is employed as an intervention method to keep at-risk individuals safe until they cease to be a danger to themselves or others. At-risk individuals may also be placed in a partial hospitalization therapy, in which the patient sleeps at home but spends most of the day in a psychiatric hospital setting. This intensive treatment usually involves group therapy, individual therapy, medication management, and is used often in the case of children and adolescents.

Medical Therapy

Serotonin reuptake inhibitors

• Fluoxetine
• Fluvoxamine
• Paroxetine
• Sertraline
• Citalopram
• Escitalopram

Serotonin-norepinephrine reuptake inhibitors

• Duloxetine
• Venlafaxine
• Desvenlafaxine
• Milnacipran
• Levomilnacipran

Tricyclic antidepressants

• Amitriptyline
• Nortriptyline
• Imipramine
• Desipramine
• Clomiprramine
• Doxepine
• Amoxepine

Monoamine oxidase inhibitors

• Phenelzine
• Tranylcipromine

Treatment failure

Treatment after monotherapy failure
(VAST-D Study)

Intervention		Outcome
Medication	Mode final dose	Remission %	Quit 2˚ ADRs (%)
Switch medications
Bupropion SR	200 mg twice daily	22.3%	10%
Augment medications
Aripiprazole	10 mg	29%	5%
Bupropion SR	300 mg daily	27%	7%

After starting medications, treatment should be switched if there is no response within one month.

When treated with monotherapy for depression, approximately 30% of patients have remission of symptoms while 50% have a response to medications.

For patients with inadequate response, randomized controlled trials provide guidance.

• The original VAST-D trial, that did not include aripiprazole, confirms that augmenting with bupropion is the most effective of options other than augmentation with aripiprazole. In this trial, either adding sustained-release bupropion ("bupropion was 200 mg per day during weeks 1 and 2, increasing to 300 mg per day by week 4 and to 400 mg per day (the final dose) during week 6") or buspirone (up to 60 mg per day) for augmentation as a second drug can cause remission in approximately 30% of patients (bupropion may be more effective than buspirone), while switching medications can achieve remission in about 25% of patients. Alternatively, "extended-release venlafaxine, the starting daily dose of 37.5 mg for 7 days was increased to 75 mg from day 8 to 14, to 150 mg from day 15 to 27, to 225 mg from day 28 to 41, to 300 mg from day 42 to 62, and to 375 mg from day 63 onward."
• The PReDICT trial found that among patients who initially were treated with either an SSRI or CBT, remission was increased when the opposite treatment (CBT or SSRI) was added to non-remitters.
• The newer VAST-D trial found that augmentation with aripiprazole is effective. The dose of aripiprazole was 2 mg of with titration to 5, 10, or 15 mg daily as guided by measurement-based care using the PHQ-9. However, aripiprazole led to more adverse drug reactions including somnolence, akathisia, and weight gain. The second most effective was augmentation with buproprion starting at 150 mg sustained release to 300 mg or 400 mg daily as guided by measurement-based care using the PHQ-9.

• More recently, mirtazapine, was found not to add to SSRIs.

Treatment after SSRI (citalopram) failure
(STAR*D Studies)

Intervention		Outcome
Medication	Mean final dose	Remission %	Quit 2˚ ADRs (%)
Switch meds (NEJM 2006; PMID: 16554525)
Bupropion SR	283 mg	21%	27%
Sertraline (SSR)	136 mg	18%	21%
Venlafaxine ER (SNRI)	194 mg	25%	21%
Augment meds (NEJM 2006; PMID: 16554526)
Bupropion SR	268 mg	30%	13%
Buspirone	41 mg	30%	21%

The STAR*D trial has reported the frequency of re-emergence of suicidality for different second levels of treatment.

In level 3 of the STAR*D trials, patients who had failed two trials of a second-generation antidepressant, tended to better with nortriptyline than mirtazapine.

Aripiprazole, originally introduced as an atypical antipsychotic agent, is approved as an adjunct to other antidepressants.

Stopping medications

Patients are generally advised not to stop taking an antidepressant suddenly and to continue its use for at least four to months to prevent the chance of recurrence. For patients that have chronic depression, medication may need to be continued for the remainder of their life.

Patients should be treated indefinitely if they have "three or more prior major depressive episodes or who have chronic major depressive disorder should proceed to the maintenance phase of treatment after completing the continuation phase."