Pharmaceutical Care of People with Depression

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

Raise awareness and promoting mental health and well-being 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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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.

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

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.

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!

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.

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.