2ObjectivesProvide an overview of the diagnosis and therapeutic management of depressionIdentify key pharmaceutical care needs of this group of patientsExplore ways of positively impacting on the care of this patient population
3Raise awareness and promoting mental health and well-being National Programme for Improving Mental Health and Well-being in Scotland SeptemberKey aims:Raise awareness and promoting mental health and well-beingEliminate stigma and discriminationPrevent suicidePromote and support recovery
4Key Facts & Figures Life-time Prevalence: 1 in 2 women; 1 in 4 men 30% of above with Major Depressive Illness>80% treated in primary care50-60% of patients respond to 1st line Treatment25-30% placebo response in controlled trials20-60% of patients respond to switching between class of antidepressant or SSRIs37% of patients relapse within 1 yr. of remission in primary care
5Depression - Diagnosis by DSM-IV criteria At least five of the following symptoms (including either 1 or 2) for two weeks andcausing clinically significant distress or impairment in functioning –Depressed moodLoss of interest or pleasure in almost all activitiesSignificant weight loss or gain, or change in appetite nearly every dayInsomnia or hypersomniaPsychomotor agitation or retardation (observable by others)Fatigue or loss of energyFeelings of worthlessness or excessive or inappropriate guiltDiminished ability to think or concentrate, or indecisivenessRecurrent thoughts of death or suicide
6Depression - At Risk Patients Adverse social circumstancesDrug and alcohol misusePhysical illnessHospitalised patientsPatients Rx musculoskeletal/CNS drugsPostnatal womenAction:refer cases of suspected undiagnosed depression
7Management Options (alone or in combination) Psychotherapy Drug therapyElectro-Convulsive TherapyAims of treatmentRemission of symptoms to the pre-morbid stateRestoration of social and working capacityReduced risk of relapse and recurrencePrevent suicide
8Choice of Antidepressant “There are no clinically significant differences in efficacy between TCAs and SSRIs.”Geddes JR, Freemantle N et alSSRIs versus other antidepressants for depressive disorderThe Cochrane Library , Issue No4, 2000Oxford: update Software (Cochrane review)
9Factors Influencing Choice Prominent features of depressionCo-existing disease statesInteracting drugsPrevious response to therapyIndividual tolerability to side effectsAbility to comply – one daily dosing may be simplerAge of patientRisk of overdosePregnancy & breast feeding- Generally SSRI 1st line but not indicated in mild depression
10Transmission Mechanisms Pre-synaptic Receptors: Control the release of neurotransmitterDrugPost-synaptic ReceptorsTransmission
11Tricyclic Antidepressants (TCAs) All act on Serotonin and NA but in different proportionsAlso hit muscarinic, 1 receptors and histamine receptors – responsible for side effectsSome more toxic in overdose than othersReserved for 3rd – 4th line these days
12Selective Serotonin Re-uptake Inhibitors (SSRIs) Serotonergic side effectsGI – Nausea, vomiting, dyspepsiaCentral – dizziness, agitation, insomnia, headacheOthers – Dry mouth, sexual dysfunction, bleeding disorders, anorexia or weight loss.Usually 1st line agentsUseful for patients with physical problems as have good side effect profile
13Monoamine Oxidase Inhibitors (MAOIs) Boost available monoamines by inhibiting breakdown by monoamine oxidase enzyme (centrally & peripherally)Irriversible inhibitors -Phenelzine, tranylcypromine, IsocarboxazidConsumption of tyramine rich foods or sympathomimetic agents results in hypertensive crisis –dietary restrictions applyMust not be prescribed with other antidepressants – washout must be observedRisks in elective surgeryReserved as 4th-5th line but useful in phobic patients or those with atypical hypochondriacal or hysterical featuresReversible inhibitors –Moclobemide- Dietary restrictions less necessary
14Venlafaxine & Duloxetine (SNRIs) Boost serotonin & NA levels by reuptake mechanismNew 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
15Mirtazapine (NaSSA)Noradrenergic and specific serotonergic antidepressantpresynaptic 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 dysfunctionAlso histaminergic – responsible for sedation and weight gainPractically no anticholinergic effects and no cardiovascular effectsRarely blood dyscrasias
16Reboxetine (NARI)Noradrenaline reuptake inhibitor (weak effect on 5HT)Side effects – insomnia, sweating, dizziness, urinary hesitancyCan be considered 2nd or 3rd line therapy as favourable side effect profile
17General Risks of Antidepressant All antidepressants can cause hyponatraemia (CSM warning)All lower seizure threshold to some extent.All can cause sweatingAll can cause “switching” in bipolar patientsDiscontinuation 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.
18The Role of the Pharmacist Reduce stigma by using a responsive pro-active approachBe responsive to possibility of undiagnosed depressionProvide information about antidepressantsPromote concordanceMonitor and provide support to patient & carersIdentify adverse effects and interactions (including non-prescribed medication)Discourage self diagnosis and treatmentSupport people at risk of suicide
19Initial Prescription for Antidepressant Reduce stigma - reassure patient depression is a common illness and most patients recoverEmphasise 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.
20Lack 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 circumstancesSwitching 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!
21Stopping 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 fluoxetineTo avoid problems –After < 8 weeks treatment withdraw over 1-2 weeksAfter 6-8 months treatment taper over 6-8 weeksAfter long term maintenance, reduce dose by 25% every 4-6 weeks.
22How to Identify and Meet the Pharmaceutical Care Needs Education checklist for first presentation or changes in dose or medicationPharmaceutical care needs assessment for depression to identify gaps in patient knowledge, effectiveness, safety and complianceImplement as part of your own CPD or local project.