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Pharmacotherapy in Psychiatry

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Slide 1 :

Pharmacotherapy in Psychiatry Depression Schizophrenia Bipolar disorders

Slide 2 :

Contents Schizophrenia and antipsychotics Depression and antidepressants Bipolar disorders and mood stabilizers

Slide 3 :

Schizophrenia and antipsychotics

Slide 4 :

Schizophrenia Characterized by psychosis, hallucinations, delusions, cognitive defects, occupational and social dysfunction Chronic psychotic illness Episodic exacerbations and remissions with residual symptoms Complete remission is not common

Slide 5 :

Schizophrenia Epidemiology Lifetime prevalence is 1% in United States Onset in late teens or early 20s in males; sometime later in females Suicide rate comparable to depressive illness (approx 10%)

Slide 6 :

Schizophrenia Etiology Exact etiology unknown Genetic predisposition Intrauterine, birth or postnatal complications Viral CNS infections Environmental stressors (biochemical or social) No evidence of association with poor parenting

Slide 7 :

Schizophrenia Pathophysiology No consistent neuropathology or biomarkers for schizophrenia ? Increased dopamine in mesolimbic pathways causes delusions and hallucinations ? Dopamine deficiency in mesocortical and nigrostriatal pathways causes negative symptoms (apathy, withdrawal) Hallocinogens produce effect through action on 5-HT2 receptors

Slide 8 :

Schizophrenia Positive symptoms Hallucinations Delusions Disordered thinking Disorganized speech Combativeness Agitation Paranoia Negative symptoms Social withdrawal Emotional withdrawal Lack of motivation Poverty of speech Blunted affect Poor insight Poor judgement Poor self-care

Slide 9 :

Schizophrenia Antipsychotics Typical / Conventional antipsychotics Atypical antipsychotics

Slide 10 :

Typical / conventional antipsychotics Chlorpromazine (Largactil®) Flupenthixol (Fluanxol®) Haloperidol (Serenace®, Haldol®) Pericyazine (Neulactil®) Pimozide (Orap®, Orap Forte®) Sulpiride (Dogmatil®) Thioridazine (Melleril®) Trifluoperazine (Stelazine®) Thiothixene (Navane®)

Slide 11 :

Typical / conventional antipsychotics Refers to agents introduced in US before 1990 Also known as “Dopamine receptor antagonists” Pharmacologic activity at blocking central dopamine receptors (esp. D2 receptors) “Neuroleptics” Due to tendency to cause neurologic Adverse effects “Major tranquilizers” Inappropriate as these agents (esp. high potency) can improve psychosis without sedating or making patients tranquil

Slide 12 :

Typical / conventional antipsychotics

Slide 13 :

Typical / conventional antipsychotics Mechanism of action Blocks receptors for dopamine, acetylcholine, histamine and norepinephrine Current theory suggests dopamine2 (D2) receptors suppresses psychotic symptoms All typical antipsychotics block D2 receptors Close correlation between clinical potency and potency as D2 receptor antagonists

Slide 14 :

Typical / conventional antipsychotics Properties Effective in reducing positive symptoms during acute episodes and in preventing their reoccurrence Less effective in treating negative symptoms Some concern that they may exacerbate negative symptoms by causing akinesia Higher incidence of EPS / sedation / anticholinergic Adverse effects

Slide 15 :

Typical / conventional antipsychotics Potency All have same ability to relieve symptoms of psychosis Differ from one another in terms of potency i.e. size of dose to achieve a given response When administered in therapeutically equivalent doses, all drugs elicit equivalent antipsychotic response

Slide 16 :

Typical / conventional antipsychotics Low potency Chlorpromazine, thioridazine Medium potency Perphenazine High potency Trifluoperazine, thiothixene, fluphenazine, haloperidol, pimozide

Slide 17 :

Typical / conventional antipsychotics

Slide 18 :

Typical / conventional antipsychotics

Slide 19 :

Typical / conventional antipsychotics

Slide 20 :

Typical / conventional antipsychotics Adverse effects Extrapyramidal symptoms (EPS) Early reactions – can be managed with drugs Acute dystonia Parkinsonism Akathisia Late reaction – drug treatment unsatisfactory Tardive dyskinesia (TD) Early reactions occur less frequently with low potency drugs Risk of TD is equal with all agents

Slide 21 :

Typical / conventional antipsychotics Adverse effects Acute dystonia Develops within a few hours to 5 days after first dose Muscle spasm of tongue, face, neck and back Oculogyric crisis (involuntary upward deviation of eyeballs) Opisthotonus (tetanic spasm of back muscles, causing trunk to arch forward, while head and lower limbs are thrust backwards) Laryngeal dystonia can impair respiration Management Anticholinergics (Benztropine, diphenhydramine IM/IV) Lower or split dosing Switch agent Add scheduled benztropine / diphenhydramine with antipsychotic

Slide 22 :

Typical / conventional antipsychotics Adverse effects Parkinsonism (neuroleptic induced) Occurs within first month of therapy Bradykinesia, mask-like facies, drooling, tremor, rigidity, shuffling gait, cogwheeling, stooped posture Shares same symptoms with Parkinson’s disease Management Centrally acting anticholinergics (scheduled benztropine / diphenhydramine / benzhexol with antipsychotics) and amantadine Avoid levodopa as it may counteract antipsychotic effects Switch to atypical antipsychotics for severe symptoms

Slide 23 :

Typical / conventional antipsychotics Adverse effects Akathisia Develop within first 2 months of therapy Compulsive, restless movement Symptoms of anxiety, agitation Management Beta blockers (propranolol) Benzodiazepines (e.g. lorazepam) Anticholinergics (e.g. benztropine, benzhexol) Reduce antipsychotic dosage or switch to low potency agent

Slide 24 :

Typical / conventional antipsychotics Adverse effects Tardive dyskinesia (TD) Develops months to years after therapy Involuntary choreoathetoid (twisting, writhing, worm-like) movements of tongue and face Can interfere with chewing, swallowing and speaking Symptoms are usually irreversible

Slide 25 :

Typical / conventional antipsychotics Adverse effects Tardive dyskinesia (TD) Management Some manufacturers suggest drug withdrawal at earliest signs of TD (fine vermicular movements of tongue) may halt its full development Gradual drug withdrawal (to avoid dyskinesia) Use lowest effective dose Atypical antypsychotic for mild TD Clozapine for severe, distressing TD Inconsistent results with Diazepam, clonazepam, valproate Propranolol, clonidine Vitamin E

Slide 26 :

Typical / conventional antipsychotics Other Adverse effects Neuroleptic malignant syndrome (NMS) Rare but serious reaction, 0.2% of patients on neuroleptics High fever, autonomic instability, mental status changes, leaden rigidity, elevated CK, WBC, myoglobinuria Management Discontinue antipsychotic Paracetamol for hyperthermia IV fluids for hydration Benzodiazepines for anxiety Dantrolene for rigidity and hyperthermia Bromocriptine for CNS toxicity

Slide 27 :

Typical / conventional antipsychotics Other Adverse effects Neuroleptic malignant syndrome (NMS) After symptom resolution Some suggest to wait for at least 2 weeks before resuming Use lowest effective dose Avoid high potency agents Consider atypical antipsychotics However, NMS has been reported from patients taking clozapine, risperidone, olanzapine and quetiapine

Slide 28 :

Typical / conventional antipsychotics Other Adverse effects Prolactinemia D2 receptor blockade decreases dopamine inhibition of prolactin Results in galactorrhea, amenorrhea, loss of libido Managed with bromocriptine Sedation Administer once daily at bedtime Seizures Haloperidol has a lower risk of seizures Anticonvulsants (beware or possible interaction with antipsychotic)

Slide 29 :

Atypical antipsychotics Refers to newer agents Also known as “Serotonin-dopamine antagonists” Postsynaptic effects at 5-HT2A and D2 receptors

Slide 30 :

Atypical antipsychotics Amisulpiride (Solian®) Quetiapine (Seroquel®) Ziprasidone (Zeldox®) Risperidone (Risperdal®) Olanzapine (Zyprexa®) Clozapine (Clozaril®) Aripiprazole (Abilify®)

Slide 31 :

Atypical antipsychotics Mechanism of action Similar blocking effect on D2 receptors Seem to be a little more selective, targeting the intended pathway to a larger degree than the others Also block or partially block serotonin receptors (particularly 5HT2A, C and 5HT1A receptors) Aripiprazole: dopamine partial agonist (novel mechanism)

Slide 32 :

Atypical antipsychotics Properties Available evidence to show advantage for some (clozapine, risperidone, olanzapine) but not all atypicals when compared with typicals At least as effective as typicals for positive symptoms May be more efficacious for negative and cognitive symptoms (still under debate)

Slide 33 :

Atypical antipsychotics Properties Less frequently associated with EPS More risk of weight gain, new onset diabetes, hyperlipidemia Novel agents, more expensive

Slide 34 :

Atypical antipsychotics Potency All atypical antipsychotics are equally effective at therapeutic doses Except clozapine Most effective antipsychotic For resistant schizophrenia 2nd line due to life-threatening side effect

Slide 35 :

Atypical antipsychotics

Slide 36 :

Atypical antipsychotics

Slide 37 :

Atypical antipsychotics

Slide 38 :

Atypical antipsychotics 1st line atypical antipsychotics All atypicals except clozapine NICE recommendations Atypical antipsychotics considered when choosing 1st line treatment of newly diagnosed schizophrenia Treatment option of choice for managing acute schizophrenic episode Considered when suffering unacceptable Adverse effects from a conventional antipsychotic Changing to an atypical not necessary if typical controls symptoms adequately and no unacceptable Adverse effects

Slide 39 :

Atypical antipsychotics 2nd line atypical antipsychotic Clozapine Most effective antipsychotic for reducing symptoms and preventing relapse Use of clozapine effectively reduce suicide risk 1% risk of potentially fatal agranulocytosis Acute pronounced leukopenia with great reduction in number of neutrophil NICE recommendations Clozapine should be introduced if schizophrenia is inadequately controlled despite sequential use of 2 or more antipsychotic (one of which should be an atypical) each for at least 6-8 weeks)

Slide 40 :

Atypical antipsychotics Clozapine BNF 52 (September 2006) Leucocyte and differential blood count normal before starting Monitor counts Q week for 18 weeks, then at least Q 2 weeks after 1 year At least Q 4 weeks after count stable for 1 year (for 4 more weeks after discontinuation) If leucocyte count < 3000/mm3, or if ANC < 1500/mm3, discontinue immediately and refer to hematologist Patient should report immediately symptoms of infection, esp. flu-like illness (fever, sore throat)

Slide 41 :

Atypical antipsychotics Clozapine Rare cases of myocarditis and cardiomyopathy Fatal Most commonly in first 2 months CSM recommendations Physical exam and medical history before starting Persistent tachycardia esp. in first 2 weeks should prompt observation for cardiomyopathy If myocarditis or cardiomyopathy, stop clozapine Inform patients for unexplained fatigue, dyspnea, tachypnea, chest pain, paipitation and ask them to report these signs and symptoms immediately

Slide 42 :

Atypical antipsychotics Clozapine Contraindication History of clozapine-induced agranulocytosis Bone marrow suppression On myelosuppressive drugs Caution Seizure disorders Diabetes

Slide 43 :

Antipsychotic oral-dispersible and solution preparations Oral-dispersible preps available for 2 atypicals Risperidone (Risperdal Quicklet®) Olanzapine (Zyprexa Zydis®) Carefully peel off packing, allow tablet to dissolve on tongue and swallow Do not break the tablet Some may be dispersed in fluids (consult manufacturer literature) Solutions available for 1 typical Haloperidol (Haldol® drops) 1 atypical Risperidone (Risperdal® solution) Very concentrated, avoid from contact with skin (dermatitis)

Slide 44 :

Antipsychotic injections Available for 2 typicals Chlorpromazine (Largactil®) Haloperidol (Haldol®) 2 atypicals Olanzapine (Zyprexa®) Ziprasidone (Zeldox®) Useful for acutely agitated patients

Slide 45 :

Antipsychotic depot injections Available for 4 typicals Haloperidol decanoate (Haldol Decanoate®) Fluphenazine decanoate (Modecate®) Flupenthixol (Fluanxol®) Zuclopenthixol (Clopixol Depot®) 1 atypical Risperidone (Risperdal Consta®) Used for chronic illness and history of noncompliance Trial of oral meds first to assess tolerability

Slide 46 :

Non-antipsychotic agents Benzodiazepines Useful in some studies for anxiety, agitation, global impairment and psychosis Schizophrenic patients are prone to BZD abuse Limit use to short trials (2-4 weeks) for management of severe agitation and anxiety Lithium Limited role in schizophrenia monotherapy Improve psychosis, depression, excitement, and irritability when used with antipsychotic in some studies

Slide 47 :

Non-antipsychotic agents Carbamazepine Weak support when used alone and with antipsychotic Alters metabolism of antipsychotic NOT to be used with clozapine (risk of agranulocytosis) Valproate Concurrent administration with risperidone and olanzapine resulted in early psychotic improvement in recent investigation Propranolol Research showed improvement in chronic aggression Treat aggression or enhance antipsychotic response Reasonable trial ? 240mg/day

Slide 48 :

Antipsychotics in schizophrenia Selection of typical antipsychotics Equally efficacious Chosen by side effect profile Atypical antipsychotics may be appropriate if Adverse effect is a particular concern Additional benefits for negative and cognitive symptoms required Clozapine 2nd line treatment when other agents are ineffective or not tolerated

Slide 49 :

Antipsychotics in schizophrenia Depot antipsychotic preparations Useful for noncompliant patients with poor insight Antidepressents and mood stabilisers In schizoaffective disorders Patients with secondary mood symptoms or aggressivity Differentiate between adverse effects and signs of disease progression E.g. Parkinsonism vs. psychotic hysteria, Akathisia vs. exacerbation of psychosis

Slide 50 :

Antipsychotics in schizophrenia Oral administration Divided daily doses at initial phase Once daily at bedtime when stabilized Promoting sleep and reducing daytime sedation Smallest effective dose employed Oral-dispersible and solution preparations For unreliable patients Injections Usually deltoid or gluteal muscle (or according to manufacturer) Depot injections At intervals of 1 to 4 weeks Generally not more than 2-3ml oily injection at one site Correct injection technique (z-track) and injection site rotation

Slide 51 :

Antipsychotics in schizophrenia Treatment response First 7 days Decreased agitation, hostility, combativeness, anxiety, tension and aggression Normalization of sleep and eating habits First 2-3 weeks Increased socialization, improvement in self-care 6-8 weeks Improvement in formal thought disorder

Slide 52 :

Antipsychotics in schizophrenia Acute phase Initiate therapy Titrate as tolerated to average effective dose Stabilization phase Dose titration within the therapeutic range Maintenance phase Therapy should be continued for at least 12 months after remission of 1st episode Good treatment responders should be treated for at least 5 years Continuous lifetime maintenance required in the majority of patients to prevent relapse Lowest effective and tolerable dose

Slide 53 :

Depression and antidepressants

Slide 54 :

Depression Depressed mood and/or decrease in interest in things that used to give pleasure Sadness severe enough or persistent enough to interfere with function DSM-IV: Major depressive disorder / major depression Dysthymia Depression for most of the day, more days than not Depressive disorder not otherwise specified Depressive disorder due to a general physical condition Substance-induced depressive disorder

Slide 55 :

Depression Epidemiology Life prevalence 3-17% Onset in late 20s Highest in 25-44 years Elderly in community Female vs male = 2:1 Female 10-25% lifetime risk Male 5-12% lifetime risk

Slide 56 :

Depression Epidemiology 4th most common reason to visit family physician Most common in elderly and difficult to diagnose Coexists with dementia or delirium frequently Recurrence rate of major depression After single episode = 50% After second episode = 70% After third episode = 90% Approx 10-15% of patients with major depressive or bipolar disorder complete suicide

Slide 57 :

Depression Signs and symptoms Depressed mood Sleep (insomnia or hypersomnia) Loss of interest (including libido) Guilt Energy loss Concentration loss Appetite (loss or gain) Psychomotor (agitation or retardation) Suicide (ideation)

Slide 58 :

Depression Etiology Etiology unknown Uncertain with heredity History of child abuse or other major life stresses Changes in neurotransmitter/neurohormone levels Cholinergic, noradrenergic/dopaminergic and serotonergic neurotransmission Deregulation with hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis and growth hormone Life stresses (e.g. Separation and losses)

Slide 59 :

Depression Pathophysiology Exact course unknown Changes in receptor-neurotransmitter relationship in limbic system Serotonin, norepinephrine, sometimes dopamine Increased pump uptake of neurotransmitter Reabsorption into neuron Destroyed by monoamine oxidase in mitochondria Lack of neurotransmitters

Slide 60 :

Antidepressants Tricyclic and related antidepressants (TCA) E.g. amitriptyline, imipramine, doxepin, mianserin, trazodone Monoamine-oxidase inhibitors (MAOI) E.g. moclobemide, phenelzine, isocarboxazid, tranylcypromine Selective serotonin reuptake inhibitors (SSRI) E.g. fluoxetine, paroxetine, sertraline, citalopram Other antidepressants E.g. mirtazapine, venlafaxine, duloxetine, flupentixol

Slide 61 :

Tricyclic and related antidepressants (TCA) Amitriptyline (Saroten®) Clomipramine (Anafranil®) Dothiepin (a.k.a. dosulepin, Prothiaden®) Doxepin (Sinequan®) Imipramine (Tofranil®) Mianserin (Tolvon®) Nortriptyline (Nortrilen®) Trazodone (Trittico®) Trimipramine (Surmontil®)

Slide 62 :

Tricyclic and related antidepressants (TCA) Mechanism of action Blocks neuronal uptake or norepinephrine and serotonin Initial response develops in 1-3 weeks Maximal response develops in 1-2 months Older tricyclics Marked anticholinergic Adverse effects Risk of cardiotoxicity Tricyclic-related drugs (e.g. trazodone) Fewer anticholinergic Adverse effects Sedation, dizziness, priapism (persistent penile erection accompanied by pain and tenderness)

Slide 63 :

Tricyclic and related antidepressants (TCA) Properties Inexpensive, generic Some with off-label use, e.g. Neuropathy with amitriptyline Refractory skin diseases with doxepin Very dangerous in overdose Life threatening Lethal dose only 8 times average daily dose Acutely depressed patients should not be given more than 1-week TCA supply at one time

Slide 64 :

Tricyclic and related antidepressants (TCA) Adverse effects Orthostatic hypotension Reduced by moving slowly when assuming upright posture Sit or lie down if symptoms (dizziness, lightheadedness) occur Divided doses and slow titration Anticholinergic effects Dry mouth, blurred vision, photophobia, constipation, urinary retention, tachycardia Tolerance may develop as treatment persists Divided doses and slow titration Sedation Dose at bedtime

Slide 65 :

Tricyclic and related antidepressants (TCA) Adverse effects Cardiac toxicity Arrhythmias and heart block ECG recommended before initiation Do not use in heart block Seizures Lowered seizure threshold Hypomania (mild mania) Elevated mood Patient should be evaluated to determine dose reduction or bipolar disorder Diaphoresis Paradoxical effect

Slide 66 :

Tricyclic and related antidepressants (TCA) Drug interactions CNS depressants Narcotics, benzodiazepines Additive CNS depression Anticholinergics Additive anticholinergic effects P450 enzyme inducers/inhibitors

Slide 67 :

Monoamine-oxidase inhibitors (MAOI) Moclobemide (Aurorix®) Not registered in Hong Kong Phenelzine Isocarboxazid Tranylcypromine

Slide 68 :

Monoamine-oxidase inhibitors (MAOI) Mechanism of action Inhibit both MAO-A and MAO-B Phenelzine, tranylcypromine Selective & reversible inhibitor of MAO-A Moclobemide

Slide 69 :

Monoamine-oxidase inhibitors (MAOI) Properties Useful in atypical depression (somnolence and weight gain), refractory disorders and certain types of anxiety disorders Less prescribed than tricyclics, SSRIs and other antidepressants Danger of dietary and drug interactions

Slide 70 :

Monoamine-oxidase inhibitors (MAOI) Properties Drug interactions Other antidepressants should not be started for 2 weeks after MAOI has been stopped (3 weeks for clomipramine or imipramine) MAOI should not be started for 7-14 days after a tricyclic or related antidepressant (3 weeks for clomipramine or imipramine) MAOI should not be started for at least 2 weeks after a previous MAOI

Slide 71 :

Monoamine-oxidase inhibitors (MAOI) Adverse effects Hypertensive crisis Severe occipital headache, photophobia, palpitation, sharply increased in BP due to additive effect between MAOI and adrenergic stimulants Tyramine-rich food e.g. cheese, wine, smoked/aged/picked meat or fish, alcohol Amphetamins Pseudoephedrine

Slide 72 :

Monoamine-oxidase inhibitors (MAOI) Adverse effects Orthostatic hypotension Insomnia Weight gain Sexual dysfunction

Slide 73 :

Selective serotonin reuptake inhibitors (SSRI) Fluoxetine (Prozac®) Fluvoxamine (Faverin®) Paroxetine (Seroxat®) Sertraline (Zoloft®) Citalopram (Cipram®) Escitalopram (Lexapro®)

Slide 74 :

Selective serotonin reuptake inhibitors (SSRI) Mechanism of action Inhibits reuptake of serotonin (5-HT) presynaptic uptake Increases availability of serotonin at synapses

Slide 75 :

Selective serotonin reuptake inhibitors (SSRI) Properties Overdose less likely to be fatal Less anticholinergic side effects But more GI side effects Seems to be better tolerated

Slide 76 :

Selective serotonin reuptake inhibitors (SSRI) Properties Fluoxetine Most stimulating SSRI Indicated for premenstrual dysphoric disorder (PMDD) (as Sarafem®) Long half-life, ensure 5 week washout before MAOI (2 week for other SSRI) Some SSRIs also indicated for Obsessive-compulsive disorder (OCD) Panic disorder Eating disorders Social phobia Post traumatic stress disorder (PTSD)

Slide 77 :

Selective serotonin reuptake inhibitors (SSRI) Adverse effects Headache GI Nausea, diarrhoea, loss of appetite Titrate dose to minimize side effect May be taken with food Anticholinergic Adverse effects Fever than TCA Tend to see more with paroxetine

Slide 78 :

Selective serotonin reuptake inhibitors (SSRI) Adverse effects Somnolence or insomnia Dose in morning for insomnia Increase in anxiety, agitation, akathisia early in treatment (esp. fluoxetine) Agitation or nervousness Sexual dysfunction

Slide 79 :

Selective serotonin reuptake inhibitors (SSRI) Adverse effects Serotonergic syndrome Rare but potentially fatal interaction between 2 or more drugs that enhance serotonin Anxiety, shivering, diaphoresis, tremor, hyperflexia, autonomic instability (BP, pulse) Fatal if malignant hyperthermia Management Mild: resolve in 24-48 hours after discontinuing offending agent Severe: 5-HT antagonist, cyproheptidine, propranolol, methysergide, dantrolene (hyperthermia)

Slide 80 :

Serotonin norepinephrine reuptake inhibitor (SNRI) Duloxetine (Cymbalta®) Venlafaxine (Efexor®, Efexor XR®) Mechanism of action Inhibits norepinephrine and serotonin reuptake Potentiates neurotransmitter activity in the CNS

Slide 81 :

Serotonin norepinephrine reuptake inhibitor (SNRI) Duloxetine (Cymbalta®) Properties and Adverse effects More potent than venlafaxine Also indicated for diabetic neuropathy Insomnia, nausea, headache

Slide 82 :

Serotonin norepinephrine reuptake inhibitor (SNRI) Venlafaxine (Efexor®, Efexor XR®) Properties and Adverse effects Also for anxiety disorders Lacks sedative and anticholinergic effects predominant with TCAs Nausea, dizziness, sexual dysfunction, hypertension (when > 300mg/day)

Slide 83 :

Mixed serotonin norepinephrine effects Mirtazapine (Mirtazon®, Remeron®, Remeron SolTab®) Mechanism of action Presynaptic a2-antagonist Increases central noradrenergic and serotonergic neurotransmission

Slide 84 :

Mixed serotonin norepinephrine effects Mirtazapine (Mirtazon®, Remeron®, Remeron SolTab®) Properties and Adverse effects Fewer anticholinergic effects Marked sedation during initial treatment Stimulating as dose increases Increased appetite and weight gain Constipation, dry mouth

Slide 85 :

Norepinephrine dopamine reuptake inhibitor (NDRI) Bupropion (Wellbutrin SR®) Mechanism of action Inhibits weakly the neuronal uptake of dopamine, norepinephrine and serotonin Does not inhibit monoamine oxidase

Slide 86 :

Norepinephrine dopamine reuptake inhibitor (NDRI) Bupropion (Wellbutrin SR®) Properties and side effects GI side effects, confusion, dizziness, headache, insomnia, tremor Seizure risk at high doses Minimal risk of sexual dysfunction Also licensed for smoking cessation (Zyban®)

Slide 87 :

Other antidepressants Flupenthixol (Fluanxol®) Typical antipsychotic Antidepressant effect at low doses Antipsychotic dose: 3-9mg twice daily Antidepressant dose: 1-3mg daily Combined with another antidepressant as Deanxit® Flupenthixol 0.5mg + melitracen 10mg For depression and anxiety

Slide 88 :

Non-antidepressants Anxiolytics Antipsychotics Use may mask the true diagnosis Used with caution But are still useful adjuncts in agitated patients Lithium and thyroid To potentiate effect of antidepressants in refractory cases Lithium: plasma level 0.4-0.8mEq/L Thyroid supplement: 25mcg/day

Slide 89 :

Antidepressants in depression Choice of agents All are equally efficacious for depression Selection based on Side effect profile Potential drug interaction Response failure to an antidepressant does not predict response to another drug class or another drug within class

Slide 90 :

Antidepressants in depression Geriatrics Reduce initial dose by half Gradual dose titration Risk of dizziness and syncope Hyponatremia Pediatrics Decrease initial dose by half Recent evidence links SSRIs with suicide in adolescents

Slide 91 :

Antidepressants in depression Treatment response Weeks 1-2 Physical responses Improvement in appetite and sleep Weeks 3-4 Energy and cognitive responses Improvement in energy Improvement in guilt, concentration Weeks 5-6 Emotional responses Improvement in mood

Slide 92 :

Antidepressants in depression Continuation therapy To prevent relapse 4-9 months after complete remission of symptoms At therapeutic doses Lifelong maintenance therapy Recommended by some investigators for patients at greater risk or reoccurrence < 40 years with = 2 prior episodes Any age with = 3 prior episodes

Slide 93 :

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Pharmacotherapy in Psychiatry. Depression; Schizophrenia; Bipolar disorders. Contents. Schizophreni more Pharmacotherapy in Psychiatry. Depression; Schizophrenia; Bipolar disorders. Contents. Schizophrenia and antipsychotics; Depression and antidepressants …www.hksne.org.hk/course/Drugs_in_Psychiatry.ppt less