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Managing Depression

ICSI 2008 Guidelines: Major depression in adults in primary care.

  1. Diagnosis
  2. Initial Therapy
  3. Medication Interactions
  4. Monitoring Response to Therapy
  5. Indications for Referral
  6. References

**PHQ-9 Depression Questionnairre [pdf]

I. Diagnosis

  • Based on DSM IV, depression includes five of the following nine symptoms daily for at least 2 weeks:
    1) Depressed mood
    2) Anhedonia
    3) Sleep disturbance
    4) Motor retardation (or agitation)
    5) Depressed appetite
    6) Poor energy
    7) Poor concentration
    8) Suicidal ideation
    9) Feelings of guilt or worthlessness
  • One of the first two symptoms must be present.
  • There must be a change from previous functioning.
  • The symptoms must cause significant impairment.
  • The symptoms must not be as a result of a medical condition or substance abuse
  • Prior to starting an antidepressant, patients should be screened for a history of mania to avoid precipitating a manic episode with initiation of therapy
  • Major depression is to be distinguished from minor depression and dysthymia

II. Initial Therapy

  • Medication or structured psychotherapy results in a 50-60% response rate in primary care.
  • Medication should be provided for patients with moderate to severe depression.
  • The efficacy of different antidepressants is generally similar.
  • The following medications can all be considered first line:
    • SSRIs
    • Desipramine
    • Nortriptylline
    • buproprion (wellbutrin)
    • mirtazapine (remeron)
    • duloxetine (cymbalta)
    • venlafaxine (effexor)
  • SSRIs are often used first given their favorable adverse effect profile.
  • Tricyclic antidepressants (eg desipramine,nortriptylline) can be fatal in overdose and can lead to somnolence.
  • Buproprion can lead to seizures.
  • Venlafaxine can lead to hypertension.
  • Mirtazapine is associated with weight gain.
  • The SSRIs are more similar than different and include:
    • citalopram (celexa) - generic
    • escitalopram (lexapro)
    • fluoxetine (prozac) - generic
    • fluvoxamine (luvox)
    • paroxetine (paxil) - generic
    • sertraline (zoloft)
  • On average paroxetine and fluoxetine are more activating than citalopram or sertraline.
  • If the sexual side effects of SSRIs are not tolerated, buproprion or venlafaxine is a good choice.

III. Medication Interactions

  • Fluvoxamine has multiple interactions through the P450 system and is generally avoided.
  • Fluoxetine is a weak inhibitor of CYP 3A4, the pathway in which PIs and efavirenz are metabolized, and can increase levels of these medications, although no clinically relevant effects have been reported.
  • The SSRIs are also substrates of CYP 2D6 and CYP 3A4 and their levels can be affected by drug interactions with PIs and efavirenz.
  • Because of their wide therapeutic window, one does not need to dose adjust the SSRI to account for these interactions.

IV. Monitoring Response to Initial Therapy

  • Antidepressants begin to take effect during the first 2-4 weeks of therapy.
  • Full therapeutic effect is generally felt after 4-6 weeks of therapy.
  • If the patient responds fully he should be continued on the same dose of medication for at least 6 months to reduce the risk of relapse.
  • 50-85% of patients with a single episode of major depression will have at least one more episode.
  • The risk of relapse is associated with the number of prior episodes of major depression, presence of co-morbid conditions, and residual symptoms between episodes of major depression.
  • The decision on whether to continue medication after six months of therapy is based on the risk of relapse, severity of depression, tolerability of medication, and patient preference.
  • If the antidepressant is stopped the dose should be tapered slowly over a number of weeks to prevent discontinuation syndrome or rebound depression.
  • If no response or only a partial response is noted after 4-6 weeks of therapy the initial diagnosis should be confirmed and adherence assessed.
  • Reasonable options include increasing the dose, referring the patient for psychotherapy, or switching the patient to a new medication.
  • If the medication dose is increased one should reassess the patient in 3-4 weeks.
  • If no effect is seen an alternative medication should be used.
  • Failure to respond to one SSRI does not predict failure to another SSRI.
  • One can safely switch from one SSRI to another without cross-tapering.
  • When switching between different antidepressant classes given the potential for discontinuation syndrome, interactions through the P450 system, or the serotonin syndrome one should consult pharmacy or the Marangell reference below for recommendations regarding the specifics of changing from one medication class to another.

V. Indications for referral

  • Many patients with depression can be managed effectively without formal consultation with psychiatry.
  • Indications for referral include:
    • An immediate threat of self-harm
    • A history or mania or psychosis
    • A lack of response to two medications
    • For those that require/desire psychotherapy.
  • At Madison Clinic, psychiatry will be happy to offer informal consultation.

VI. References

American Psychiatric Association, Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, American Journal of Psychiatry157:4 April 2000 supplement.

American Psychiatric Association, Practice Guidelines for the Treatment of Patients with HIV/AIDS, American Journal of Psychiatry 157:11 November 2000 supplement.

Marangell, Lauren, Switching Antidepressants for Treatment-Resistant Depression, Journal of Clinical Psychiatry 2001; 62 (suppl 18).

Whooley, Mary A, Managing Depression in Medical Outpatients, NEJM 2000; 343:1942-1950.


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