1 / 48

Antidepressants and mood stabilizers

Antidepressants and mood stabilizers. Agenda. Mode of action Classification Properties Indications and contrindications Principles of administration Side effects. Antidepressant medications. Psychotropic agents effective in different kinds of mood (depressive) disorders

denisehernandez
Download Presentation

Antidepressants and mood stabilizers

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Antidepressants and mood stabilizers

  2. Agenda • Mode of action • Classification • Properties • Indications and contrindications • Principles of administration • Side effects

  3. Antidepressant medications • Psychotropic agents effective in different kinds of mood (depressive) disorders • Idiopathic depresion • Depresion during the course of other mental disorders • (i.e. post-psychotic depression) • Symptomatic depression during the course of neurologic or somatic illnessess

  4. Types of antidepressants and pathogenesis of depression • 60s’-90s’ of the XXth century: modification of brain • NA, DA, 5-HT systems: • Schildkraut (1965): model of catecholamine insufficiency -noradrenaline (NA) and dopamine (DA) • Lapin i Oxenkrug (1969) serotonine (5-HT) insufficiency Introduction of IMAO and tricyclic antidepressants into clinical practice: • IMAO – (irreversible) inhibition of monoamine oxidase (never used in Poland) • tricyclic antidepressants: imipramine, amitryptyline, clomipramine

  5. Types of antidepressants and pathogenesis of depression • SSRI: selective serotonine reuptake inhibitors (block of 5HT active transport through presynaptic membrane) • Selective NA block: reboxetine • Influence on DA system: bupropion • The agents with double mode of action: • SNRI –serotonine and noradrenaline reuptake inhibitors: venlafaxine • NaSSA – noradrenaline and serotonine specific agents: mirtazapine

  6. Types of antidepressants and pathogenesis of depression • Tianeptine: brain neurogenesis stimulation and influence on intracellular regulation of neuronal plasticity through modification of genomic transcription • Agomelatine: circadian rhytm regulation (regulation of secretion of cortisol, prolactine, melatonine)

  7. Classification of antidepressant medications • A. Inhibitors of reuptake monoamine transport (NA, DA, 5HT) • B. Agents of other modes of action • C. IMAO & other medications acting on monoaminergic systems • D. Agents with other properties • (i.e. tianeptine, agomelatine) • E. Other compunds used in mood disorders • hypericum- in mild depressive episode • omega-3 fatty acids, vitamin D: augmentation of antidepressants

  8. A. Inhibitors of reuptake monoamine transport- TCA • Effect: increase of NA, DA, 5HT in synapses and activation of NA and 5HT systems in brain • Tricyclic antidepressants (TCA) – unselective NA & 5HT reuptake inhibitors • amitryptyline • desipramine • clomipramine • nortriptyline • doxepine

  9. A. Inhibitors of reuptake monoamine transport - TCA • Clomipramine: the most intense affinity to 5-HT • Dezipramine, nortryptyline: the most intense affinity to NA • Other receptor binding and actions: antycholinergic, antyhistamine, α1-adrenergic blockade, ion channel blockade • Metabolism through CYP 450 • TCA are not medications of first choice in the treatment of depression, especially mild and moderate • Indications for TCA: depressive episodes of substantial intensity with anxiety/insomnia • Amitryptyline and clomipramine: analgesic (antinociceptive) properties • Clomipramine: effective in OCD

  10. A. Inhibitors of reuptake monoamine transport - TCA • Dosage: 100-300 mg/day (average 150 mg/day) • Contraindications: narrow angle glaucoma, cardiac arrythmia, unstable coronary artery disease/heart infarct, hypertension, prostate hypertrophy, hyperthyroidism, Addison disease, delirium, intoxication with drugs of adrenergic and cholinergic properties • Common early TCA side effects: somnolence, dryness in mouth, accomodation disturbances, ortostatic hypotonia, dysuria. These symptoms often disappear after few weeks of treatment. • Complications due to TCA: • psychiatric: CENTRAL CHOLINERGIC SYNDROME, phase switch (into mania), psychotic symptoms • neurologic: tremor, myoclonia, epileptic attacks • somatic: atrial fibrillation, anuria, glaucoma attack.

  11. B. SSRI • Currently used SSRI: • Fluoxetine • Fluwoxamine • Sertraline • Paroxetine • Citalopram • Escitalopram • Properties: • antidepressive, antiobsessive, antianxiety

  12. B. SSRI • Fluoxetine • The most intense (in comparison with other SSRI) activation of the postsynaptic 5HT2c receptors (weight decrease- transient) • T0,5: 2 days!! For fluoxetine (7 days!! for norfluoxetine– main metabolite) • CYP2D6 i CYP3A4 inhibition • Dose: 20-60 mg/day Fluvoxamine • Sigma receptor stimulation (sedative properties) • T0,5: 15 hours • CYP1A2 i CYP2C19 inhibition • Dose: 100-300 mg/day

  13. B. SSRI • Sertraline • Blockade of dopamine transporter (beneficial effect on cognitive functions and Parkinsonism) • T1/2: 26 godz. • CYP450- mild inhibition • Dose: 50-200 mg/day Paroxetine • Antipanic properties • T0,5: 15 hours • CYP2D6 – strong inhibition • Dose: 20-60 mg/day • Should be withdrawed gradually!

  14. B. SSRI • Citalopram • QTc prolonongation in old age • Effective in mild and moderate depression • Cyp 450 – weak inhibition • Dose: 20-60 mg/day Escitalopram • Possible QTc prolonongation in old age • The most effective SSRI? • Action on two 5HT transporter sites (primary and allosteric) • Cyp450 – mild inhibition • Dose: 10-20 mg/day

  15. B. SSRI • Indications for SSRI administration: • Depressive disorders spectrum • Anxiety disorders • OCD: doses greater than treatment of depression • Bulimia: fluoxetine, sertraline • Premenstrual dysphoric disorder: constantly or during the second phase of cycle

  16. B. SSRI: side effects • Gastrointestinal: nausea, appetite decrease, stomach discomfort • Tension, insomnia or somnolence • Sexual dysfunctions: disturbances of ejaculation and orgasm, libido decrease • During long-term treatment: • Decrease of bone density in older age • Increase risk of gastrointestinal bleeding • Disturbances of electrolytes’ balance

  17. C. IMAO & RIMA • Monoaminooxidase inhibitors • Since 50s’ of the XXth century’ primarily: unselective and irreversible; many side effects, dietary restrictions • In 90s of the XXth century– RIMA (Reversible Inhibitor of Monoamine Oxidase – A): MOCLOBEMIDE • Indications: depression with psychomotor retardation, poststroke depression, depression in Parkinson disease • Dose: 300-600 mg/day • Should not be administered with: SSRI, clomipramine, pethidine, sympathomimetic and antimigrenic medications • Side effects: headache, blood pressure fluctuations, arrythmia

  18. C. Other medications acting on monoaminergic systems • Agents influencing mainly noradrenergic activity: • Mianserine • Stimulation of NA system through alpha-2 autoreceptors; antagonism against 5HT2 • Indications: depression of different intensity , insomnia • Dose: 60-90 mg/day • Side effects: somnolence, WEIGHT GAIN, • leucopenia, hepatotoxicity, epileptic seizures Reboxetine • Selective inhibitor of noradrenaline transporter • Indications: mild and moderate depression with motor retardation • Dose: 4-8 mg/day • Could be co-administered with SSRI • Side effects: restlessness, insomnia, sweating, tachycardia, dysuria

  19. C. Other medications acting on monoaminergic systems • Agents acting mainly on serotoninergic system • Trazodone • Mode of action: inhibition of serotonine transporter and blockade of 5HT2 receptors (SARI – serotonine antagonist and reuptake inhibitor) and influence on alpha-2 adrenergic receptors • Indications: depression with anxiety or restlessness, insomnia • Dose: 50-300 mg/day • Side effects: somnolence, headache, vertigo, gry mouth, hypotonia (rarely: leucopenia, priapism, hepatotoxicity)

  20. C. Other medications acting on monoaminergic systems • Agents with dual activity: SNaRI – serotonin and norepinephrine reuptake inhibitors (selective influence on NA i 5HT, without affinity to other receptors, as contrary to TCA) • Venlafaxine • indications: depression (especially with motor retardation), anxiety disorders • dose: 75-375 mg/day (depending on the intensity of depression) • antinociceptive properties • side effects: restlessness, phase switch, insomnia, tremor, blood pressure rise, sexual dysfunctions, epileptic seizures

  21. C. Other medications acting on monoaminergic systems • SNARI • Milnacipram • indications: depression of different intensity • dose: 100-200 mg/d, (twice a day) • side effects: nausea, vertigo, insomnia, sweating, dysuria Duloxetine • indications: depression of different intensity • antinociceptive properties (may be used in fibromyalgia) • dose: 60-120 mg/d (once a day) • side effects: nausea, vertigo, somnolence or insomnia, sexual dysfunctions

  22. C. Other medications acting on monoaminergic systems • NaSSA (noradrenergic and selective serotonergic antidepressant) • Mirtazapine • Mode of action: influence on NA and α2 receptors blockade plus 5HT2 i 5HT3 receptors blockade • Indications: moderate and severe depression especially with insomnia • Dose: 15-45 mg/d before sleep • Side effects: sedation, vertigo, dry mouth, constipation, appetite increase, WEIGHT GAIN

  23. C. Other medications acting on monoaminergic systems • Vortioxetine • Modulation of 5HT and blockade of serotonine transporter • Efficacy in treatment of depression • Side effects: mild- nausea; • (not influence sexual functions) • Procognitive properties: beneficial influence on cognitive functions in patients with depression

  24. C. Other medications acting on monoaminergic systems • Agents influencing mainly dopaminergic system • Buproprion • Mode of action: inhibition of DA transporter (also inhibition of NA transporter, to a lesser degree) • First registration- as a compund for nicotine dependence (Zyban) then as an antidepressant (Wellbutrin) • Indications: depression with motor retardation, anhedonia and somnolence • dose: 150-450 mg/d • Side effects: insomnia, dry mouth, epileptic seizures • (does not influence sexual functions and weight)

  25. D. Agents with other properties • Tianeptine • Stimulation of serotonine reuptake • Indications: mild and moderate depression • dose: 37,5 mg/d (3x12,5 mg) • Side effects: vertigo, dry mouth • Agomelatine • Mode od action: stimulation of melatoninergic receptors M1 i M2, • 5HT2c serotoninergic receptors blockade • Clinical effects: circadian rhytm normalisation • dose: 25 mg-50 mg before sleep • Side effects: vertigo, dyspepsia, • aminotranspherase elevation- hepatotoxicity • (does not influence sexual functions and weight)

  26. Principles of antidepressants’ administration • Consider therapeutic effect and safety of treatment • Selection of AD adequately to the intensity of depression • Consider configuration of symptoms i.e. anxiety, motor retadation, restlessness, insomnia, obsessions, suicidality, age, effectiveness of previous treatment with AD, side effects, comorbidity • Unsuccessfull AD treatment increases the risk of relapse or recurrence • Most favourable balance of efficacy and tolerance in moderate depression: escitalopram and sertraline (Ciprani i wsp. 2009) • Tretament of severe depression: medications with double mode of actions, i.e. TCA, venlafaxine, mirtazapine or two AD of synergic activity

  27. Principles of treatment with antidepressants • Improvement: after 2-4 weeks • Insufficient response: increase the dose after 2 weeks to maximum, if lack of significant improvement after 4-6 weeks: change of AD • Treatment of (unipolar) depressive episode: at least six months after attaining remission • After 6month treatment 50% patients with first episode had depression remitted, however in patients with third or more episode- only 1/3 persons achieved remission • (Rybakowski et al. 2003) • Persons with second recurrence of depression in period of three years should be treated with AD • for at least 5 years

  28. Principles of treatment with antidepressants • BIPOLAR DEPRESSION • The greatest risk of phase switch: in type 1 bipolar disorder • AD may provoke phase switch • (especially increased risk: TCA, venlafaxine, bupropion) • less risky- AD with sleep promoting properties: trazodone, agomelatine, mirtazapine PSYCHOTIC DEPRESSION: treatment with AD is insufficient, institution of neuroleptic is mandatory (electroconvulsive therapy may be considered)

  29. Principles of treatment with antidepressants • SSRI • in I trimester of pregnancy– increased risk of fetal heart malformations, • in II-III trimester increased risk of premature labour and Apgar score decrease SSRI during breast feeding: • All psychotropics pass into milk; • lower risk– paroxetine and sertraline

  30. Treatment-resistant depression • Lack of efficacy of two or more correctly conducted courses of therapy • Managing refractory depression: 1. Change for AD with different mode of action (switching) 2. Combination of two ADs 3. Adding medication other than AD (augmentation) for potentialisation of effect of an antidepressant • Mood stabilizer, neuroleptic, buspiron, thyreostatic

  31. Combined treatment in refractory depression 1. SSRI + NA-compound (desipramine, mianserine, reboxetine) 2. AD + compound influencing 5HT1receptors (buspiron) 3. AD + triiodotyronine or thyroxine 4. AD + omega-3 FA in large doses 5. AD+ lithium (3-fold increase of chance for improvement) – combination more effective in bipolar than unipolar affective disorder 6. AD + mood stabilizer (carbamazepine, lamotrigine) 7. AD+ atypical neuroleptic (olanzapine, aripiprazole, risperidone, quetiapine) Beware: „treatment-resistance depresion” may be in fact bipolar depression Consider electroconvulsive therapy in refractory depression

  32. Mood stabilizer • effective in acute mania and/or depression • prophylactic (stoppping reccurences) • for at least one year • not induce worsening in any significant areas of bipolar disorder symptoms

  33. Mood stabilizers' classification • 1. Ist generation mood stabilizers • Lithium salts (LIT) • Valproate (VAL) • Carbamazepine (CBZ) 2. IInd generation mood stabilizers - Clozapine (CLO) - Olanzapine (OLA) - Quetiapine (QUE) - Aripiprazole (ARP) - Risperidone (RIS) - Ziprasidone (ZIP) - Lamotrigine (LAM)

  34. LITHIUM • First psychotropic medication ever • One of basic medications in bipolar disorder prophylaxis • Antidepressive effect and potentialisation of antidepressants • Antisuicidal • In 1 out of 3 patients with bipolar 1 disorder full remission for at least 20 years on lithium monotherapy; lithium combination with other mood stabilizer or other mood stabilizer monotherapy is reccomended in remainder bipolar 1 patients • Therapeutic lithium levels: • 0,5-0,8 mmol/l : in prophylaxis • 0,8-1,2 mmol/l: in treatment of mania • Side effects: tremor, dyspepsia, leucocytosis, polydypsia, polyuria, hypothyroidism (10%), dermatological symptoms • Intoxitation: above2 mmol/l • gastrointestinal, motor, and brain symptoms

  35. VALPROATE • In maniacal mixed state valproate is more effective than lithium • Similar efficacy of valproate and lithium in mania treatment • Rapid valproate dose elevation in mania treatment is possible • Side effects: vomitting, tremor, ataxia, weight gain, hair loss, potential hepatotoxicity • Contraindicated in women with childbearing potential • Therapeutical serum level: 50-100 ug/ml

  36. CARBAMAZEPINE (CBZ) • Effective both in mania and in bipolar disorder prophylaxis • Greater efficacy in comparison with lithium in atypical bipolar disorder • CBZ especially reccommended in patients with temporal lobe abnormalities in EEG • Side effects: nausea, vertigo, ataxia, nystagmus, agranulocytosis, Stevens-Johnson syndrome • Therapeutical serum level: 4-8 ug/ml

  37. IInd generation mood stabilizers • Clozapine (CLO) • Treatment with CLO is associated with the risk of agranulocytosis and therefore it is used only in refractory bipolar patients • Co-administration of CLO and lithium may decrease leucopenia risk • Other side effects: WEIGHT GAIN, hyperglycaemia, dyslipidemia, sialorrhea, somnolence, constipation, QTc prolongation • Olanzapine (OLA) • Equally effective as lithium and valproate in prophylaxis of bipolar episodes; more effective than lithium in mania prevention • Side effects: WEIGHT GAIN, hyperglycaemia, dyslipidemia • Quetiapine • Effective in treatment of mania • Effective in bipolar depression • Slight extrapyramidal symptoms • Side effects: weight gain, somnolence

  38. IInd generation mood stabilizers • Risperidone - antimanic and potentialization of antidepressants in refractory depression • Ziprasidone - antimanic and potentialization of antidepressants in refractory depression • Aripiprazol - partial D2 agonist, influence on 5HT1a & 5HT2 - monotherapy for 2 years prevents maniacal episodes • Lamotrigine - more effective against depression than against mania - more effective than lithium in prevention of depression - effective in: rapid cycling bipolar disorder, BD with substance abuse, BD with anxiety • compulsory slow dose elevation: for 4-6 weeks • side effects: Stevens-Johnson syndrome

  39. Application of mood stabilizers • Intramuscular injections– olanzapine, aripiprazole, ziprasidone • mania of great intensity- at least two mood stabilizers • maniacal mixed states– valproate, atypical neuroleptic or combination of both • hypomania – monotherapy with Ist generation mood stabilizer or with atypical neuroleptic • Bipolar I depression– mood stabilizer (+ AD for limited time) • Bipolar II depression– monotherapy with AD is allowed, but mood stabilizer is reccomended • Mild or moderate bipolar depression– mood stabilizer with antidepressive properties (lithium, quetiapine, lamotrigine) or add another mood stabilizer to one already used. AD may be added when this is ineffective • Depressive mixed state AD should be avoided • Suicidal bipolar patient: lithium, clozapine, ECT • Patients with organic brain changes: antiepileptic medications (CBZ, VPA, lamotrigine)

  40. ELECTROCONVULSIVE THERAPY • ECT • Introduced to psychiatry in 1938 by Cerletti and Bini • Current practice: • administered under anesthetic with a muscle relaxant • patient has no memory of both electric shock application and seizure • highly effective, relatively safe

  41. ECT biologic effects • ECT induced seizure is associated with: • Oxygen intake increase • Glucose metabolism increase • Blood-brain barrier permeability increase • Calcium elimination with urine increase and simultaneous its decrease in cerebrospinal fluid • DA activity increase and cholinergic activity decrease • Adrenergic receptors sensitivity increase and serotoninergic receptors density increase • Transient increase of serum adrenaline, noradrenaline, prolactin, vasopressin, oxitocine, ACTH, GABA, cortisol, endorphines, insuline and LH

  42. ECT: indications • Depressive disorders: • Depression with intensive suicidal ideations and attempts • Depression with stupor in a patient at risk of dehydratation due to anorexia • Severe psychotic depression • Depression with extreme restlessness • Severe depression with significant somatic illness when administration of psychotropis medication is not possible

  43. ECT: indications Acute fatal catatonia Acute mania (with sensory disturbance) in patients with contraindications to or inefficacy of psychotropic treatment, especially when a patient is at risk of exhaustion due to extreme restlesness or psychophramacologic treatment is associated with high risk of somatic complications

  44. ECT: indications • Second-line treatment of: • Refractory depression • Chronic depression in a mood disorder • Depression in old age especially with comorbid somatic illnesses • Mood disorder, schizophrenia or schizoaffective psychosis exacerbation during pregnancy • Catatonic schizophrenia • Refractory schizophrenia (with exception of chronic stable schizophrenia) • Neuroleptic malignant syndrome

  45. ECT contraindications: rigorous Illnesses with elevated intracranial pressure Recent myocardial infarction Recent intracranial bleeding

  46. ECT contraindications: relative • Huge aneurysm of blood artery or aorta • Detached retina • Phaeochromocytoma • Vein thrombosis • Glaucoma with narrow angle • Focal brain damage • Illnessess associated with increased risk of general anesthesia • ECT inefficacy in previous treatment • significant side effects during present course of ECT

  47. ECT: general information • Internist and anaesthesiologic consultation before performing ECT is required • Electrodes may be placed uni or bilaterally • Seizure threshold is lower in males than in females, higher in older age, lower in mania than in depression, higher in dehydratation and after each subsequent procedure • Number and frequency: • 4-12 procedures in depression, 12-20 in schizophrenia, • 2-3 times a week in depression and schizophrenia • up to 2-3 times a day in catatonia, acute mania and severe depression

  48. ECT: complications • Death: 2 ot of 100.000 patients treated • Myocardial infarction, ventricular fibrillation, cardiac arrest, cardiovascular failure, aneurysm rupture • Apnoe, laryngeal cramp • Epileptic state • Memory disturbance • Headeaches, muscle pain, nausea, vomitting

More Related