Pharmaceutical Care of People with Depression

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• Pharmaceutical Care of People with Depression

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Objectives

• Provide an overview of the diagnosis and
  therapeutic management of depression
• Identify key pharmaceutical care needs of this
  group of patients
• Explore ways of positively impacting on the care
  of this patient population

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National Programme for Improving Mental Health
and Well-being in Scotland September 2003-2006

• Key aims
• Raise awareness and promoting mental health and
  well-being
• Eliminate stigma and discrimination
• Prevent suicide
• Promote and support recovery

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Key Facts Figures

• Life-time Prevalence 1 in 2 women 1 in 4 men
• 30 of above with Major Depressive Illness
• gt80 treated in primary care
• 50-60 of patients respond to 1st line Treatment
• 25-30 placebo response in controlled trials
• 20-60 of patients respond to switching between
  class of antidepressant or SSRIs
• 37 of patients relapse within 1 yr. of remission
  in primary care

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Depression - Diagnosis by DSM-IV criteria

• At least five of the following symptoms
  (including either 1 or 2) for two weeks and
  causing clinically significant distress or
  impairment in functioning
• Depressed mood
• Loss of interest or pleasure in almost all
  activities
• Significant weight loss or gain, or change in
  appetite nearly every day
• Insomnia or hypersomnia
• Psychomotor agitation or retardation (observable
  by others)
• Fatigue or loss of energy
• Feelings of worthlessness or excessive or
  inappropriate guilt
• Diminished ability to think or concentrate, or
  indecisiveness
• Recurrent thoughts of death or suicide

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Depression - At Risk Patients

• Adverse social circumstances
• Drug and alcohol misuse
• Physical illness
• Hospitalised patients
• Patients Rx musculoskeletal/CNS drugs
• Postnatal women
• Action
• refer cases of suspected undiagnosed depression

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Management

• Options (alone or in combination)
• Psychotherapy
• Drug therapy
• Electro-Convulsive Therapy
• Aims of treatment
• Remission of symptoms to the pre-morbid state
• Restoration of social and working capacity
• Reduced risk of relapse and recurrence
• Prevent suicide

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Choice of Antidepressant

• There are no clinically significant differences
  in efficacy between TCAs
• and SSRIs.
• Geddes JR, Freemantle N et al
• SSRIs versus other antidepressants for depressive
  disorder
• The Cochrane Library , Issue No4, 2000
• Oxford update Software (Cochrane review)

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Factors Influencing Choice

• Prominent features of depression
• Co-existing disease states
• Interacting drugs
• Previous response to therapy
• Individual tolerability to side effects
• Ability to comply one daily dosing may be
  simpler
• Age of patient
• Risk of overdose
• Pregnancy breast feeding
• - Generally SSRI 1st line but not indicated in
  mild depression

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Mechanisms
Pre-synaptic Receptors Control the release of
neurotransmitter
Drug
Post-synaptic Receptors
Transmission
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Tricyclic Antidepressants (TCAs)

• All act on Serotonin and NA but in different
  proportions
• Also hit muscarinic, ?1 receptors and histamine
  receptors responsible for side effects
• Some more toxic in overdose than others
• Reserved for 3rd 4th line these days

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Selective Serotonin Re-uptake Inhibitors (SSRIs)

• Serotonergic side effects
• GI Nausea, vomiting, dyspepsia
• Central dizziness, agitation, insomnia,
  headache
• Others Dry mouth, sexual dysfunction, bleeding
  disorders, anorexia or weight loss.
• Usually 1st line agents
• Useful for patients with physical problems as
  have good side effect profile

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Monoamine Oxidase Inhibitors (MAOIs)

• Boost available monoamines by inhibiting
  breakdown by monoamine oxidase enzyme (centrally
  peripherally)
• Irriversible inhibitors -Phenelzine,
  tranylcypromine, Isocarboxazid
• Consumption of tyramine rich foods or
  sympathomimetic agents results in hypertensive
  crisis dietary restrictions apply
• Must not be prescribed with other antidepressants
  washout must be observed
• Risks in elective surgery
• Reserved as 4th-5th line but useful in phobic
  patients or those with atypical hypochondriacal
  or hysterical features
• Reversible inhibitors Moclobemide
• Dietary restrictions less necessary

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Venlafaxine Duloxetine(SNRIs)

• Boost serotonin NA levels by reuptake
  mechanism
• New monitoring guidelines for venlafaxine
  baseline ECG and blood pressure. Not to be used
  if cardiac risk factors present. ECG BP
  monitoring on therapy.
• Some evidence to support high doses (225mg) in
  treatment resistant depression. Still used in
  secondary care. Associated with raised BP.
• Side effects include nausea, insomnia, agitation,
  restlessness, ECG changes, hypertension,
  withdrawal effects (even with missed doses)
• Duloxetine does not have the same monitoring
  requirements but not much experience with it yet

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Mirtazapine (NaSSA)

• Noradrenergic and specific serotonergic
  antidepressant
• presynaptic ?2 antagonist increases NA and
  serotonin levels centrally but post synaptically
  blocks 5HT2 and 5HT3 subtypes so there is a
  specific action on 5HT1. Less sleep disturbance
  and less sexual dysfunction
• Also histaminergic responsible for sedation and
  weight gain
• Practically no anticholinergic effects and no
  cardiovascular effects
• Rarely blood dyscrasias

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Reboxetine (NARI)

• Noradrenaline reuptake inhibitor (weak effect on
  5HT)
• Side effects insomnia, sweating, dizziness,
  urinary hesitancy
• Can be considered 2nd or 3rd line therapy as
  favourable side effect profile

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General Risks of Antidepressant

• All antidepressants can cause hyponatraemia (CSM
  warning)
• All lower seizure threshold to some extent.
• All can cause sweating
• All can cause switching in bipolar patients
• Discontinuation reactions can occur with all
  antidepressants, but are more common in short
  half life agents regardless of class.
• Combinations of antidepressants are potentially
  risky and should be used only under specialist
  supervision.
• Switching drugs should be carried out with care.

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The Role of the Pharmacist

• Reduce stigma by using a responsive pro-active
  approach
• Be responsive to possibility of undiagnosed
  depression
• Provide information about antidepressants
• Promote concordance
• Monitor and provide support to patient carers
• Identify adverse effects and interactions
  (including non-prescribed medication)
• Discourage self diagnosis and treatment
• Support people at risk of suicide

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Initial Prescription for Antidepressant

• Reduce stigma - reassure patient depression is a
  common illness and most patients recover
• Emphasise lag period side effects often present
  before benefit, encourage to persevere.
• Discuss discontinuation reactions but reassure
  that medication is not addictive. Do not stop
  abruptly.
• For SSRIs ensure GP has discussed side effects
  patient should report any increase in suicidal
  thoughts or increase in agitation or anxiety (may
  be indicative of akathisia). Discuss common side
  effects of any antidepressant.
• Ensure patient aware of expected duration of
  treatment.
• Result Improved concordance, reduced potential
  for relapse.

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Lack of Response/Switching

• Ensure adequate trial. Where some response a
  dose increase may be considered.
• Usually switch to a different class is indicated,
  but can switch within a class in certain
  circumstances
• Switching guidelines
• In theory it is better to stop and washout one
  drug before starting another (must do this with
  MAOIs)
• In practical terms this is rarely possible if
  patient is ill.
• Potential problems with cross tapering include
  antidepressant discontinuation effects,
  interactions between the 2 drugs e.g. some SSRIs
  increase TCA levels, serotonin syndrome
  (potentially life threatening), cholinergic
  effects.
• If in doubt seek specialist advice!

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Stopping antidepressants

• If stopped abruptly discontinuation symptoms may
  include
• Headaches, restlessness GI symptoms, flu like
  symptoms, abdominal cramps, sleep disturbance,
  anxiety, agitation electric shock sensations
  (particularly with SSRIs)
• Common with short half life drugs, rare with
  fluoxetine
• To avoid problems
• After lt 8 weeks treatment withdraw over 1-2 weeks
• After 6-8 months treatment taper over 6-8 weeks
• After long term maintenance, reduce dose by 25
  every 4-6 weeks.

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How to Identify and Meet the Pharmaceutical Care
Needs

• Education checklist for first presentation or
  changes in dose or medication
• Pharmaceutical care needs assessment for
  depression to identify gaps in patient knowledge,
  effectiveness, safety and compliance
• Implement as part of your own CPD or local
  project.