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1IBSNBDPMPHZ▯PG▯ %FQSFTTJPO Shiromi Patrick shiromi.patrick21@ic.ac.uk0#+&$5*7&4▯ • Describe how depression presents • Use diagnostic tools for depression • Describe the pathophysiology of depression • Explain the mechanism of drugs used to treat depression • Recognise the side effects and contraindications of these drugs Plan for today Pathophysiology Prescribing What is depression? Medications$VSUJT▯/BTI▯ • 47, male • Low mood • “Can’t seem to enjoy anything anymore” à Anhedonia • Low self-esteem • Sleep difficulties • Inability to think clearly • Duration of symptoms: 1 month+%JBHOPTJT▯PG▯%FQSFTTJPO Q1: How many symptoms must be present and for how long? A. At least 6 symptoms gradually presenting over 2 weeks B. At least 4 symptoms during the same month C. At least 5 symptoms during the same 2 weeks D. At least 6 symptoms during the same month E. At least 4 symptoms presenting over 3 or more weeks%JBHOPTJT▯PG▯%FQSFTTJPO Q1: How many symptoms must be present and for how long? A. At least 6 symptoms gradually presenting over 2 weeks B. At least 4 symptoms during the same month C. At least 5 symptoms during the same 2 weeks D. At least 6 symptoms during the same month E. At least 4 symptoms presenting over 3 or more weeks For summative %JBHOPTJT▯PG▯%FQSFTTJPO • 5 or more symptoms during the same 2-week period • At least one of the symptoms must be either (1) low mood or (2) anhedonia • Other symptoms: • Weight loss or weight gain, or decrease or increase in appetite • Insomnia or hypersomnia • Fatigue or loss of energy • Feelings of worthlessness or excessive guilt • Suicidal ideation • Indecisiveness, inability to think or concentrate %JBHOPTJT▯PG▯%FQSFTTJPO • Patient Health Questionnaire 9 (PHQ-9): used to screen for depression • Patient’s score: 14 • Patient’s problem: Moderate depression.BOBHFNFOU▯PG▯%FQSFTTJPO Therapeutic objectives: Management: 1. Improve mood 1. Counseling, CBT 2. Help with sleep difficulties 2. Self-help 3. Improve his self-esteem 3. Medications 4. Improve his ability to think clearly 5. Help with everyday life Plan for today Pathophysiology Prescribing What is depression? Medications1BUIPQIZTJPMPHZ▯PG▯%FQSFTTJPO Note: 5-HTP = derived from tryptophan 5-HT = Serotonin SERT = 5-HTT1BUIPQIZTJPMPHZ▯PG▯%FQSFTTJPO For summative .POPBNJOF▯)ZQPUIFTJT Reduced levels of the monoamines serotonin, norepinephrine and/or dopamine in the CNS underpin the pathophysiology of depression Plan for today Pathophysiology Prescribing What is depression? Medications.FEJDBUJPOT▯GPS▯%FQSFTTJPO SSRIs Venlafaxine Mirtazapine4FMFDUJWF▯4FSPUPOJO▯3FVQUBLF▯ *OIJCJUPST▯ Examples: sertraline, citalopram, fluoxetine Target: serotonin transporter Location: pre-synaptic neuron Effect: increase serotonin availability in the synapse 443*T▯▯4JEF▯FGGFDUT GI disturbance – nausea, diarrhoea Sexual dysfunction Anxiety Insomnia • Act on other • Increase in • SSRI effects on • Activation of serotonin serotonin = serotonin 2C serotonergic 5- receptors too interference with receptors = HT2 receptors and • Stimulation of testosterone and increased anxiety increased serotonin dopamine and fear noradrenergic and receptors 3 and 4 dopaminergic = increased GI neurotransmission motility443*T▯▯1IBSNBDPLJOFUJDT o Reduction in depression ratings plateaus after a certain dose o Number of dropouts increases with increasing dose443*T▯▯1IBSNBDPLJOFUJDT o Reduction in depression ratings plateaus after a certain dose o Number of dropouts increases with increasing dose7FOMBGBYJOF▯▯.FDIBOJTN▯PG▯"DUJPO o Venlafaxine: SNRI – serotonin and noradrenaline reuptake inhibitor o Target: serotonin transporter, noradrenaline transporter o Location: pre- synaptic neuron 7FOMBGBYJOF▯▯4JEF▯FGGFDUT GI disturbance – Sexual dysfunction Anxiety Insomnia nausea, diarrhoea • Act on other • Increase in • SSRI effects on • Activation of serotonin serotonin = serotonin 2C serotonergic 5- receptors too interference with receptors = HT2 receptors and • Stimulation of + HYPERTENSIONosterone and increased anxiety increased serotonin dopamine and fear noradrenergic and receptors 3 and 4 dopaminergic = increased GI neurotransmission motility.JSUB[BQJOF▯▯.FDIBOJTN▯PG▯"DUJPO § Antagonist at alpha- 2-adrenergic receptors = increased release of serotonin and noradrenaline § Antagonist at central 5HT2 receptors = leaves 5HT1 receptors unopposed = antidepressant effect.JSUB[BQJOF▯▯.FDIBOJTN▯PG▯"DUJPO WHY? Mirtazapine drug targets • Sedation: H1 Highest affinity Histamine (H1) receptor Sedation receptor actions Alpha-2 receptor Anti-depressant effect are mostly ¯ excitatory Lowest affinity 5HT2 receptor Anti-depressant effect • Anti-depressant 5HT3 receptor Anti-emetic effect effect: alpha-2 receptors inhibit the release of norepinephrine .JSUB[BQJOF▯▯.FDIBOJTN▯PG▯"DUJPO Efficacy: ability of a Affinity: Determines drug molecule to strength of binding of Specificity: ability to produce an effect the drug to the bind to the desired once bound to a receptor receptor receptor.JSUB[BQJOF▯▯1IBSNBDPLJOFUJDT Mirtazapine drug targets Highest affinity Histamine (H1) receptor Affinity: high for Sedation H1, lower for 5HT2 Alpha-2 receptor Anti-depressant effect ¯ Specificity: low Lowest affinity 5HT2 receptor Anti-depressant effect 5HT3 receptor Anti-emetic effect Efficacy: antagonist so no efficacy.JSUB[BQJOF▯▯4JEF▯FGGFDUT Mirtazapine drug targets § Weight gain Highest affinity Histamine (H1) receptor Sedation § Low probability ¯ Alpha-2 receptor Anti-depressant effect of sexual 5HT2 receptor Anti-depressant effect dysfunction Lowest affinity 5HT3 receptor Anti-emetic effect § May exacerbate REM sleep behaviour disorder Plan for today Pathophysiology Prescribing What is depression? Medications1SFTDSJCJOH Switching medications Contraindications4XJUDIJOH▯NFEJDBUJPOT • Washout required before starting a new drug • Must be gradually decreased on discontinuation • Otherwise: • Serotonin syndrome • Interactions • Withdrawal • Relapse Extra Info 4FSPUPOJO▯4ZOESPNF • Cause: too much serotonin in the CNS • Culprits: overdose or therapeutic dose of serotonergic drugs • Features: triad of - neuromuscular excitation, autonomic effects, and altered mental status • Signs: hyper-reflexia, clonus, hypertonia • Other symptoms: anxiety, tachycardia, tremors, shivering, sweating&$(▯1SBDUJDF▯&$(▯1SBDUJDF▯ QTc is prolonged if > 440ms in men or > 460ms in women%SVH▯*OUFSBDUJPOT46.."3:▯ Diagnosis Pathophysiology • DSM-5 Criteria • Serotonin production, release and reuptake system in the synapse • care9 for screening in primary • Targets for medication Medications Interactions – Side effects • SSRIs • QT prolongation • Venlafaxine • Gradual dose decrease on • Mirtazapine discontinuation 2VFTUJPO▯▯▯'FFECBDL▯ Which of the following effects of mirtazapine would occur Correct answer: C first with a low starting dose? Mirtazapine has a higher affinity for H1 receptors than for alpha-2, 5HT2 and A. Anti-depressant effect 5HT3 receptors. B. Anti-emetic effect C. Sedative effect At a low dose, mirtazapine will bind H1 receptors more strongly and therefore induce sedation. 2VFTUJPO▯▯▯'FFECBDL▯ Mariah, a 61-year-old woman presents to GP with low Given the patient’s age and symptoms, mood, weight gain, joint pains and difficulty sleeping. Which the list of potential diagnoses includes would be most appropriate depression as well as other conditions such as perimenopause/menopause, action? hypothyroidism and osteoarthritis. Therefore, more investigations are needed before any medication can be prescribed. 2VFTUJPO▯▯▯'FFECBDL▯ Lewis is a 55-year-old man who struggles with low mood Venlafaxine: can cause hypertension at and anhedonia. The GP diagnoses moderately severe higher doses so need to be careful in depression. Lewis is also patients with uncontrolled struggling to control his blood hypertension pressure and has not been taking his tablets regularly. Mirtazapine: consider weight gain side Which of the following effect in the context of his hypertension medications would be more appropriate to prescribe? Citalopram: can cause serotonin syndrome and therefore hypertension, but this is a rare complication. 2VFTUJPO▯▯▯'FFECBDL▯ Kara is a 46-year-old woman who presents with anhedonia, Venlafaxine: can cause hypertension at sleeping difficulties, appetite changes and low mood. The GP higher doses – need to evaluate patient diagnoses moderate depression and is considering prescribing Mirtazapine: consider weight gain side an anti-depressant. Two effect in the context of pre-diabetes months ago, Kara saw the GP again for a check up and was Sertraline: can cause sleeping informed she has pre-diabetes. Which of the following difficulties medications would be more appropriate to prescribe? 2VFTUJPO▯▯▯'FFECBDL▯ A patient presents to hospital after fainting on his way to Correct answer: Citalopram and work. An ECG is performed erythromycin which shows a prolonged QT interval. Both can prolong the QT interval and should not be prescribed together. Which medication combination is the most likely cause of this finding?5)"/,▯:06▯ Please fill in the Feedback form! QR code Name: Shiromi Patrick Email: shiromi.patrick21@ic.ac.uk