Treatment of Depression with Medication

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Treatment of Depression with Medication
Peter Amann, MD Caring for ME Depression in
Primary Care Program Training Sponsored by MMC
Physician Hospital Organization
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First - Use the PHQ-9 to Determine if Treatment
is Indicated

• Score of 2 or greater on either of the first two
  questions is a positive screen for depression
• Scores for completed PHQ-9
• 0-4 no depression
• 5-9 possible depression with minimal symptoms
• 10-14 mild depression
• 15-19 moderate depression
• 20-27 severe depression
• Moderate depression medication psychotherapy
  are equally effective
• Severe depression medication is indicated, with
  or without psychotherapy.

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How you can use the PHQ-9

• The first two questions are validated as a screen
  for depression.
• The PHQ is validated as a way to diagnose
  depression.
• The PHQ is also validated as a measure of
  response to treatment over time.

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Guideline for Using the PHQ-9 for Initial
Management
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Options for Treatment

• Watchful waiting
• A reasonable first choice for depression with
  minimal to mild symptoms, effective in about 1/3
  of patients
• Pharmacotherapy
• Most effective treatment for severe depression
  and dysthymia (chronic depression)
• Psychotherapy
• Equally effective to pharmacotherapy for mild to
  moderate depression
• Effective as an adjunct to pharmacotherapy for
  severe depression

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Involve the Patient in the Decision

• Patients often have a preference whether to
  choose medication or psychotherapy as initial
  treatment
• Patient involvement in the decision making
  process promotes adherence
• Establishing attainable goals in partnership with
  patients may improve outcomes

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If Medication is the Appropriate Treatment

• Start with Selective Serotonin Re-uptake
  Inhibitors (SSRIs)
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Citalopram (Celexa)
• Sertraline (Zoloft)
• Escitalopram (Lexapro)
• All SSRIs are similarly effective

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Most common SSRI Side Effects (present in 5 or
more of patients)

• Nausea/diarrhea
• Sexual dysfunction (25 to 35)
• Headache
• Weight gain
• Insomnia, unusual dreams
• Nervousness, restlessness
• Concentration problems

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Less Common SSRI Side Effects (present in less
than 5 of patients)

• Dry Mouth
• Drowsiness
• Dizziness
• Sweating
• Seizures (0.1 - 0.2)
• Blurred vision / dry eyes
• Bradycardia
• Hyponatremia (in elderly patients)
• Hypomania (avoid antidepressants without mood
  stabilizer in patients with known or suspected
  bipolar disorder)
• Restless legs
• Mania
• Serotonin Syndrome (details on next slide)

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What is Serotonin Syndrome?

• Medication-induced excessive stimulation of the
  serotonergic system
• Symptoms include lethargy, restlessness,
  confusion, flushing, diaphoresis, tremor,
  myoclonic jerks
• May result in renal failure and death
• Rare when SSRIs are used alone. More common when
  SSRIs are used in combination with MAOIs.

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Bupropion (Wellbutrin)

• First line alternative to SSRIs
• Good choice for patients concerned about sexual
  side effects or have experienced sexual side
  effects on an SSRI
• More activating than SSRIs
• May help patients with attention deficit disorder
• Less likely to cause weight gain
• May be effective for smoking cessation
• May induce seizures in persons with seizure
  disorder
• Should not be used in patients who have anorexia
  or abuse alcohol

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Additional anti-depressant medications

• Other agents (multiple actions)
• duloxetine (Cymbalta)
• venlafaxine (Effexor)
• mirtazapine (Remeron)
• Tricyclic antidepressants (TCAs)
• imipramine (Tofranil)
• amitriptyline (Elavil)
• nortriptyline (Pamelor)
• MAO inhibitors (rarely used by PCPs)

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Other Antidepressants
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Tricyclic Antidepressants

• One study showed high-dose TCAs 70-80 effective
  in severely depressed inpatients
• More common side effects result in poorer
  adherence than SSRIs
• Avoid in patients with suicidal ideation or
  substance abuse

• Disadvantages
• Lethal in overdose
• Sexual dysfunction
• Weight gain
• Anticholinergic
• Sedation
• Constipation
• Dry mouth

• Advantages
• Low cost
• Long clinical history
• Subset efficacy
• Chronic pain (amitriptyline)
• Migraine headaches

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Dosing Information

• If patient is elderly or has co-morbid panic or
  anxiety start low, titrate slowly
• Assess every few weeks
• When using TCAs, can check blood levels to
  adjust dose
• Titrate dose with goal of achieving remission
• Monitor postural blood pressure changes
• See final page for specific dosing and titration
  guidance

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Length of Treatment

• For a first episode of depression, studies
  indicate rate of relapse is lower when a patient
  continues medication for 6-12 months
• For subsequent episodes of depression, 1-2 years
  of treatment or longer-term medication may be
  indicated

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Effectiveness

• 50-60 of patients respond to first medication
• 80 will respond to medication after 2-3 trials
• Lower percentage will experience complete
  remission of symptoms

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Interpreting Follow Up Scores
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How often should the PHQ be done for management
of a patient with depression?

• Once a month until the patient reaches remission
  (score 0-4) or for the first 6 months of
  treatment
• Every 3 months after that while the patient is on
  active treatment
• Once a year for people with a history of
  depression who are no longer on active treatment

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Changing Medication

• If increasing dose of initial medication does not
  provide remission
• Consider switching to another SSRI
• Some patients may respond to another drug of the
  same class
• Consider switching to a different class of
  medications
• Some authors recommend switching to another class
  as the best option if an SSRI has failed
• Carefully observe warnings of drug-drug
  interactions, and be conscious of washout times
  when changing or adding medication

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Augmentation TherapyAdding a drug that is not
an antidepressant

• Most data from randomized clinical trials involve
  lithium added to TCAs
• Many report patients improving when lithium is
  added to SSRIs
• Patients often respond to dosages of lithium
  lower than needed to treat bipolar disorder
• Starting lithium dose 300mg at bedtime
• Other possible options include
• thyroid (T3) supplementation
• Stimulants amphetamine, methylamphetamine - only
  used to treat depression as augmentation

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Augmentation Therapy Continued

• Treating insomnia increases likelihood of
  response to the antidepressants
• Some activating medicines (e.g. Venlafaxine,
  Buproprion, Fluoxetine) are best dosed in the
  morning
• At bedtime consider adding trazodone (25-200 mg)
  this medication is not habit-forming and can be
  titrated up to effect (note small risk of
  priapism)
• Alternativley, consider low dose lorazepam or
  clonezapam (0.5 2.0 mg) Taper after 7 to 10
  days.
• Anxiety
• Consider mirtazapine because of its sedative
  properties
• Lorazepam (0.5-1.0 mg tid) Alprazolam (0.25-0.5
  mg tid), clonezapam (0.5-1.0 mg bid)
• Given as scheduled dose may decrease risk of
  addiction
• These medicaions may cause worsening of
  depression
• Buspirone (5-15 mg bid or tid) if history of
  substance abuse or benzodizepines contraindicated

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Combination TherapyTwo antidepressants with
different mechanisms

• SSRI-TCA combinations reported to be effective
  for patients who do not respond to monotherapy
• Some SSRIs can cause tricyclic levels in the
  blood to rise
• SSRI-Bupropion combination may be effective
  monitor for agitation

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Addressing Side Effects

• GI distress - often resolves in 1-2 weeks, take
  with food
• Anticholinergic/dry mouth or eyes - increase
  hydration, use sugarless sweets, artificial tears
• Sedation - take medication in evening or switch
  to more activating medication (e.g., bupropion)
• Weight gain - avoid paroxetine and mirtazapine

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Dealing with Sexual Side Effects May occur in up
to 35 of patients

• Reduce dose of antidepressant
• May result in fewer symptoms without diminution
  of benefit
• There may be no therapeutic dose that reduces
  symptoms
• Switch to a medication with fewer sexual side
  effects
• Bupropion, mirtazapine
• Add a drug that may act as an antidote
• Bupropion (75-150mg/day) or sildenafil (Viagra)
  as needed
• Consider stopping antidepressant for 1-2
  days/week to allow a drug holiday- However, may
  result in relapse or non-compliance
• Switching from one SSRI to another is not
  reported to alleviate sexual side effects

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STAR D Trial

• Largest (4000 patients) and longest (7 yr) trial
  to assess effectiveness of depression treatment
  ever
• Sponsored by NIMH
• 4 levels of treatments to assess remission from
  depression patients had the options of moving
  on to additional Levels if they did not achieve
  remission

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STAR D Trial Level 1 - Celexa

• 1 in 3 patients achieved remission mean dose of
  treatment 42 mg/day and mean duration was 47 days
• Highly educated, currently employed, married
  Caucasian women with few complication psychiatric
  or medical disorders were more likely to achieve
  remission

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STAR D Trial Level 2

• Add-on Wellbutrin, Buspar or cognitive therapy
• 1 in 3 achieved remission
• Switch to Zoloft, Wellbutrin, Effexor or
  cognitive therapy
• 1 in 4 achieved remission
• Overall 50 remission after 2 Levels

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STAR D Trial Level 3

• Add-on lithium or triiodothyronine (Cytomel)
• 1 in 5 achieved remission
• Switch to Remeron or Nortriptyline
• 1 in 5-6 achieved remission

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STAR D Trial Level 4

• Stop other medications
• Start an MAOI or combination Effexor / Remeron
• 1 in 10-12 achieved remission
• Overall 70 remission after 4 Levels

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Key Messages to Promote Adherence

• Take the medication every day
• It may take 2 to 4 weeks for therapeutic
  response, longer for full effect
• Continue to take the medication even after you
  start to feel better
• Do not stop taking the medication without
  checking in with your primary care office

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Psychiatric Referral or ConsultMay be needed
when

• Two medications have failed
• Bipolar disorder is suspected
• High risk of suicidality
• Questions about diagnosis
• Co-morbid psychiatric conditions that complicate
  treatment, such as PTSD or substance abuse

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Summary

• Start with an SSRI or bupropion, unless the
  patient has had successful treatment with another
  antidepressant in the past
• Increase dose if response is not good after 4
  weeks.
• Change medication if response is not good after 8
  12 weeks
• Consider combination or augmentation treatment
  for those without good response if changing
  medication does not work
• Consider psychiatric consult for persistent
  symptoms or in other complicated situations

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References

• Materials adapted from
• Osser and Petterson, www.mhc.com/Algorithms
• MacArthur Initiative Toolkit, www.depression-prima
  rycare.org
• Other key references
• Rush, STARD What have we learned?, American
  Journal of Psychiatry, 2/07, pp.201-204
• STARD website - http//www.edc.gsph.pitt.edu/star
  d/