1. Pharmaceutical Care of People with Depression

2. 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

3. Raise awareness and promoting mental health and well-being
National Programme for Improving Mental Health and Well-being in Scotland September
Key aims:
Raise awareness and promoting mental health and well-being
Eliminate stigma and discrimination
Prevent suicide
Promote and support recovery

4. Key Facts & Figures Life-time Prevalence: 1 in 2 women; 1 in 4 men
30% of above with Major Depressive Illness
>80% 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

5. 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

6. 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

7. 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

8. 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)

9. 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

10. Transmission Mechanisms
Pre-synaptic Receptors: Control the release of neurotransmitter
Drug
Post-synaptic Receptors
Transmission

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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.

18. 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

19. 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.

20. 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!

21. 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 < 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.

22. 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.