Psychotherapeutic Drugs Lecture 5

Psychotherapeutic Drugs Psychotherapeutic drugs are described for their effects of relieving symptoms of mental illness that include Schizophrenia Mania Depression Anxiety Drugs for these disorders are Palliative i.e. alleviate without curing Psychotherapeutic D...

Psychotherapeutic Drugs Psychotherapeutic drugs are described for their effects of relieving symptoms of mental illness that include Schizophrenia Mania Depression Anxiety Drugs for these disorders are Palliative i.e. alleviate without curing Psychotherapeutic Drugs These drugs are for major mental illnesses and not for trivial indications where simpler drugs do equally as well Commencing treatment Minimise side effects Allow gradual build up to an optimal dose Treatment May be long term or intermittent depending on the severity and type of condition Compliance Psychotherapeutic Drugs Many medically used drugs can produce psychiatric symptoms at therapeutic doses (rare) and when abused. Examples Depression Methydopa (Aldomet ®), Clonadine (Catapress®) and some beta blockers e.g. propanalol (Inderal®). Psychosis, euphoria, depression Corticosteriods e.g. Betemethasone (Celestone Chronodose® inj) Confusion disorientation, depression Atropine, Benztropine Antipsychotics Antipsychotics Used primarily in the management of psychotic disorders to ameliorate abnormal behaviour, thoughts and perceptions. These medications have sedating and tranquilising effects that make them useful in severely agitated or disturbed patients Antipsychotics Amisulphride (Solian®) Olanzapine (Zyprexa®) Aripiprazole (Abilify®) Paliperidone (Invega®) Chlorpromazine (Largactil®) Pericyazine (Neulactil®) Clozapine (Clopine®) Quetiapine (Seroquel®) Droperidol (Droleptan®) Risperidone (Risperdal®) Flupenthixol (Flunaxol®) Trifluperazine (Stelazine®) Fluphenazine (Modecate®) Ziprasidone (Zeldox®) Haloperidol (Serenace®) Zuclopenthixol (Clopixol®) Classification Traditionally antipsychotics have been classified as typical or 1st generation (older) or atypical or 2nd generation (newer) Not a useful classification as both groups Similar modes of action Similar side effect profiles Older medications were classified according to chemical structure, however not helpful for the newer antipsychotics In clinical practice – termed as high potency and low potency Mechanism of action Antipsychotic action involves blockade of CNS dopamine receptors in the mesolimbic pathways All effective antipsychotics block D2 receptors. The affinity for these receptors correlates with the effective dose of the drugs Mechanism of action Many antipsychotics also block serotonin 5HT2A and 5HT2C receptors and may antagonise other receptors α1 - adrenoreceptors Histamine H1 receptors This does not effect their efficacy in psychotic illness but can produce unwanted side effects Receptor affinities of some antipsychotics Note: some older FGA show some preference for D2 over D1 Some of the newer SGA agents are highly selective for D2 Indications Acute and chronic psychosis Acute mania & maintenance of bipolar disorder Organic psychosis (e.g. dementia – associated agitation) Severe behavioural disturbances in children Tourette's syndrome & other chorea's Some other indications Adjunct in anaesthesia e.g. Droperidol Adjunct in treatment of alcoholic hallucinations e.g. Haloperidol Intractable nausea & vomiting e.g. Haloperidol, Droperidol Intractable hiccup (if non-drug treatment fails) e.g. Chlorpromazine Common adverse effects All antipsychotics have Anticholinergic effects some degree of Blurred vision anticholinergic activity EXCEPT Dry Mouth Amisulphride Constipation Aripiprazole Paliperidone Urinary hesitance or retention Risperidone Ziprasidone Sedation Orthostatic hypotension – due to the blockade if the Alpha- receptors which may lead to syncope and falls EPSE *as with all medications there are individual differences in tolerability and occurrence of adverse effects Common adverse effects http://www.uspharmacist.com/content/c/10207/?t=alzheimer%27s_and_dementia,psychotropic_disorders Common adverse effects Extrapyramidal effects (EPSE) Acute dystonia Muscle spasm of face, neck, tongue, jaw and/or hands Hyperextension of the neck & trunk, arching of the back Can interfere with walking, talking or swallowing Dystonia's include Torticollis Carpopedal spasm Trismus Perioral spasm Oculogyric crisis Common adverse effects Drug induced Parkinsonism Similar to Parkinson’s Disease Shuffling gait Drooling Tremor Increased rigidity (cogwheel) or Bradykinesia Akinesia has also been reported Usually develops after week-months of treatment Usually reversible Treated with anticholinergics or using an alternative medication Common adverse effects Akathisia Motor restlessness Person feels unable to sit/stand still, feels urgent need to move, pace, rock or tap foot Can also present at apprehension, irritability & general uneasiness Often confused with worsening agitation More common in females Usually occurs 2-3 days (up to several weeks) after starting treatment and may subside spontaneously Common adverse effects Tardive Dyskinesia Characterised by abnormal movements of the mouth, face, tongue Lip smacking Tongue darting, licking movements Constant chewing movements Sucking Grunting Sometimes abnormal movements head, neck trunk or limbs May appear after medium to long term treatment May be irreversible/no cure Common adverse effects Endocrine effects More common in women Due to dopamine receptor blockade – leads to  prolactin release which may cause Gynecomastia Galactorrhoea Amenorrhoea Anovulation Impaired spermatogenesis  libido Impaired sexual arousal Impotence Anorgasmia Common adverse effects Effect due to hyperprolactinaemia Dose dependent Associated with all antipsychotic drugs except Aripiprazole Clozapine Quetiapine Hyperprolactinaemia more likely with Amisulphride Paliperidone Risperidone Typical antipsychotics Common adverse effects Weight Gain Most antipsychotics can cause weight gain Especially – Clozapine, Olanzapine and Quetiapine Less in – Amisulpride, Aripiprazole, Ziprasidone http://primarypsychiatry.com/augmentation-strategies-in-the-treatment-of-major-depressive-disorder/ Common adverse effects Metabolic Syndrome Schizophrenia and other mental illnesses are an independent risk factor for diabetes Most antipsychotics increase this risk Clozapine and Olanzapine are especially associated with Abnormal glucose tolerance  Serum lipids Infrequent or rare adverse effects Neuroleptic Malignant Syndrome Rare Coarse tremor Catatonia Potentially fatal Characterised by Fever (>38oC) Marked muscle rigidity Altered consciousness Autonomic instability (tachycardia, tachypnoea, urinary &faecal incontinence  serum creatine kinase concentrations and leucocytosis Infrequent or rare adverse effects ECG changes Some antipsychotics can prolong the QTc interval which can lead to life threatening arrhythmias (torsades de pointes) Especially: Amisulphride, Droperidol, Haloperidol, Ziprasidone Certain individuals are more susceptible Age/gender (female) Left ventricular failure Recent cardio conversion Electrolyte imbalances Hypomagnesaemia Hypokalaemia Hypocalcaemia Hepatic dysfunctions https://www.kg-ekgpress.com/ecg_web_brain_DEMO_-_chapter_7_-_qt_interval/ Pharmacokinetics Most antipsychotic drugs are Highly lipophilic Highly protein bound Relationship between plasma concentration and effect is highly variable – therefore need to tailor the dose 40% non response rate Some have erratic and unpredictable absorbency Diagram shows range of peak plasma concentrations v’s dosages in 14 patients Note: one patient showed no response Pharmacokinetics Most antipsychotic drugs enter foetal circulation and breast milk, therefore should be avoided in pregnancy Neonatal side effects include Dystonic reactions Sedation Withdrawal Most have long half lives (t1/2) Dosage forms Tablets Capsules Liquid preparations Depot injections Fluphenazine (Modecate®) Haloperidol (Haldol®) Fluphenthixol (Fluanxol Depot®) Zuclopenthixol; Zuclopenthixol Acetate (Clopixol Acuphase®) Zuclopenthixol deconoate (Clopixol depot®) Parenteral Haloperidol Droperidole (Droleptan®) Chlorpromazine (Largactil®) Dosage forms Clozapine Used in treatment of patients non responsive to, or intolerant of other antipsychotics Able to relieve +ve and –ve symptoms Antagonist at D1, D2, D4 and 5HT2 receptors Cancause profound orthostatic hypotension accompanied by cardiac or respiratory failure. Therefore need medical supervision & resuscitation facilities when started Clozapine Associate with severe side effects; Blood Dyscrasias Other side effects Hyperpyrexia (5%) Nausea and vomiting Drowsiness (40% of treated people) Tachycardia Hypersalivation (can cause aspiration pneumonia) Weight gain Seizures Priapism Clozapine Precautions; Parkinson’s disease Epilepsy Respiratory failure Hypothyroidism Shock Closed angle glaucoma, increase intraocular pressure, GI obstruction Urinary retention Low WCC or previous blood abnormality Elderly require lower starting doses Anticholinergic Drugs Anticholinergic Drugs Anticholinergic drugs can be used to treat a variety of conditions. Many different types of anticholinergic drug, but they all work by blocking the action of acetylcholine, a type of neurotransmitter. Blocking this neurotransmitter inhibits involuntary muscle movements and various bodily functions. Anticholinergics are regularly used in psychiatric practice to counteract the extrapyramidal symptoms secondary to antipsychotic drugs Some extrapyramidal side effects (e.g. drug induced Parkinsonism, akinesia, dystonia) may be decreased by anti-parkinsonian drugs with anticholinergic action Anticholinergic Drugs Anticholinergic drugs block muscarinic receptors & reduce relative excess of cholinergic activity that accompanies dopamine deficiency Drugs Include Benztropine Benzhexol Biperidin Orphenadrine Antidepressants Monoamine theory of depression States that depression is caused by functional deficit of monoamine transmitters at certain sites in the brain, while mania results from a functional excess Early observations found that Depletion of monoamines NA and 5HT in the neuronal synapses of the brain cause depression Drugs that ↑ the availability of these monoamines would be effective in relieving depression Monoamines & their metabolites are reduced in depressed patients *Interestingly, the direct biochemical effect of antidepressants is rapid BUT the antidepressant effects can take weeks to develop Antidepressants Monoamine theory of depression Tricyclic antidepressants (TCAs) Monoamine Oxidase Inhibitors (MAOIs) Selective Serotonin Reuptake Inhibitors (SSRIs) Other antidepressants Duloxetine (Cymbalta®) Mianserin (Lumin®) Mirtazapine (Avanza®) Moclobemide (Aurorix®) Reboxetine (Edronax®) Venlafaxine (Efexor®) Sites of action of antidepressants Selectivity of monoamine uptake inhibitors for Noradrenaline (NA) & Serotonin (5HT) Tricyclic antidepressants Mode of action: Block amine pump i.e. block the neuronal reuptake of noradrenaline and serotonin into presynaptic terminals. Also block other receptors Alpha1 adrenergic Histaminergic Cholinergic Serotonergic Tricyclic antidepressants Indications: Major depression Nocturnal enuresis, urge incontinence Adjunct in pain management ADHD (third line treatment) Migraine prophylaxis Clomipramine also indicated for Obsessive-compulsive disorder Cataplexy associated with narcolepsy Tricyclic antidepressants Common adverse effects these appear early by therapeutic response is usually delayed Anticholinergic effects Sedation Dry mouth Due to H1 block Blurred vision Tolerance develops with time  Lacrimation Orthostatic hypotension Constipation (esp. in elderly) Due to α1 block Urinary hesitance or retention Others  GI motility Loss of libido and other sexual side effects Anticholinergic delirium Tremor Confusion Dizziness Agitation Anxiety Common adverse effects - TCAs Infrequent adverse effects - TCAs Cardiovascular effects Slowed cardiac conduction Especially in high doses T wave inversion pr flattening Arrhythmias Sinus Tachycardia Others Hyperglycaemia Gynaecomastia in males Breast enlargement & galactorrhoea in females Manic episodes TCA Overdose Cardiovascular toxicity Leading cause of death in OD Death have occurred in children with low doses TCAs have a direct cardiac depressing action similar to class 1 antiarrhythmics Cardiac toxicity & hypotension – difficult to manage ECG QRS complex is prolonged QT interval is prolonged due to prolongation of the QRS complex Withdrawal Syndrome TCAsmust be withdrawn slowly to avoid discontinuation syndrome May develop Cholinergic rebound Runny nose Hypersalivation Diarrhoea Abdominal cramping Sleep disturbances Monoamine Oxidase Inhibitors (MAOI) Include Phenelzine (Nardil®) Tranylcypromine (Parnate®) Mode of action Bind irreversibly to monoamine oxidase (enzyme), responsible for the breakdown of the biogenic amine neurotransmitters; Noradreanline Dopamine Serotonin Monoamine Oxidase Inhibitors (MAOI) Indications: Major depression (2nd Line) Some anxiety disorders (including phobic and panic disorders (2nd Line) Common Adverse effects Orthostatic hypotension Weight gain Sleep disturbances (especially insomnia – not given after 3pm) Agitation Impotence Rare Hypertensive Crisis Monoamine Oxidase Inhibitors (MAOI) The most important side effect is HYPERTENSIVE CRISIS (which may result in death) A sudden paroxysmal rise in in BP may occur It is usually associated with foods containing tyramine (or some drug interactions) The metabolism of some amine drugs e.g. Sympathomimetic drugs, is inhibited by MAOIs; may lead to a dangerous rise in BP which may lead to intracranial bleeding and death. Sympathomimetics are found in many cough mixtures and decongestants including nasal drops Phenyephrine e.g. Demazin® Pseudoephedrine e.g. Sudafed® Dextromethophan e.g. Benadryl dry® Monoamine Oxidase Inhibitors (MAOI) Foods rich in tyramine may elicit the reaction Tryamine found in many foods (Particularly foods that contain aged proteins) Matured cheese Yeast extracts e.g. Vegemite Pods and broad beans Fermented or aged foods such as salami, pate, dried sausage Red wine, beer Sour cream Soy bean extracts e.g. Tofu Causes release of certain biogenic amines in the body Since MAOIs inhibit the breakdown of the amines →↑ BP →Death Danger of interaction persists 2-3 weeks after MAOI discontinued Monoamine Oxidase Inhibitors (MAOI) Moclobemide (Aurorix®) Competitively & reversibly inhibits monoamine oxidase Not related to other antidepressants Original MAOIs act non-selectively on MAO-A and MAO-B Irreversible inhibition Moclobemide is relatively selective for type A Monoamine oxidase Moclobemide  the metabolism of Noradrenaline, serotonin & dopamine   concentrations of these neurotransmitters. Moclobemide (Aurorix®) Indications Mood disorders, panic disorders and social phobia Advantages Not sedative Low tryamine diet not usually required Relatively nontoxic in overdose & less likely to cause sexual dysfunction than MAOIs Common side effects Nausea, dry mouth, constipation, diarrhoea, anxiety, restlessness, insomnia, dizziness & headache. Selective Serotonin Reuptake Inhibitors (SSRIs) Include Citalopram (Cipramil ®) Escitalopram (Lexapro®) Fluoxetine (Lovan®, Prozac®) Fluvoxamine (Faverin®, Luvox®) Paroxetine (Aropax®) Sertraline (Zoloft®) Mode of Action Selectively block the reuptake of serotonin into presynaptic terminals. Have little affinity for dopamine, acetylcholine, histamine or adreno-receptors Selective Serotonin Reuptake Inhibitors (SSRIs) Indications Mood disorders (Major Depression) Anxiety disorders (OCD, Panic disorder) Bulimia nervosa Premenstrual dysphoric disorder Common side effects Nausea, diarrhoea, tremor, agitation, headache, sweating, insomnia, drowsiness, weight loss or gain, sexual dysfunction, rhinitis * Less cardiovascular, anticholinergic & sedating adverse effects than TCAs SSRI comparative information Selective Serotonin Reuptake Inhibitors (SSRIs) Serotonin Syndrome Serotonin toxicity due to  serotonin concentrations at synapse  hyper-stimulation of 5HT receptors Symptoms – a clinical triad of abnormalities Cognitive effects Mental confusion, hypomania, hallucinations, agitation Autonomic effects Fever, hypertension, tachycardia, nausea Somatic effects Muscle twitching, hyper-reflexia Serotonin Syndrome - (SSRIs) May occur if Changing antidepressants with inadequate ‘washout’ period High dose of single drug When more than one serotonergic agent used together Serotonin toxicity Warrants stopping implicated agent promptly May be serious Deaths have occurred Potential interactions Numerous and difficult to predict May inhibit liver cytochrome P450 enzyme that metabolises many drugs e.g. Fluoxetine inhibits CYP2D6 which effects the metabolism of metoprolol etc. Selective Serotonin Reuptake Inhibitors (SSRIs) Should not be given with reversible or irreversible MAOIs May cause serotonin toxicity If transferring from SSRI to reversible MAOI must let at least 5 half lives elapse before MAOI started Selective Serotonin Reuptake Inhibitors (SSRIs) Taper slowly over several weeks Symptoms of withdrawal Nausea Dizziness Anxiety Paraesthesia Agitation Sweating Tremor Confusion Electric shock like sensations Withdrawal symptoms more likely with Paroxetine & least likely with Fluoxetine Mianserin Indication - Major depression Tetracyclic antidepressant that shares most TCA properties Mode of action Antagonist α1-adrenergic H1 – histaminergic Serotonin receptors Has little anticholinergic effect Common side effects Sedation, dry mouth, dizziness, vertigo Can cause weight gain, blood dyscrasias (neutropenia, agranulocytosis) Mirtazapine (Avanza®, Mirtazon®) Indication - Major depression Closely related to Mianserin in structure so should be avoided in patients intolerant to Mianserin Mode of action Blocks post-synaptic serotonin 5HT2A, 5HT2c and 5HT3 receptors Blocks pre-synaptic central α2-adrenergic inhibitory receptors Common side effects Sedation, weakness, increased appetite, weight gain, peripheral oedema Reboxetine (Edronax®) Indication - Major depression Mode of action Inhibits noradrenaline reuptake Weakly inhibits serotonin reuptake Common side effects Urinary retention, insomnia, constipation, dry mouth, headache, paraesthesia,  in diastolic BP,  heart rate, sweating Venlafaxine (Efexor®) Indications - Major depression, generalised anxiety, social phobia, panic disorder Mode of action Inhibits serotonin and noradrenaline reuptake Common side effects Sweating, dizziness, anorexia, anxiety, nausea, rash, tremor, vomiting, hypertension More toxic than SSRIs in overdose – may cause arrhythmias, ECG changes & seizures, fatalities have occurred Adverse effects of Antidepressants Adverse effects of Antidepressants General Principles Evidence suggest that all are approximately equal in efficacy but response can vary markedly in patients First line drugs TCAs SSRIs Mirtazapine Moclobemide TCAs, MAOIs and Venlafaxine more toxic in overdose than other first line treatment TCAs & Mirtazapine often cause weight gain Some improvement in symptoms in 1-3 weeks but full antidepressant effect in 6-8 weeks Drugs used in Bipolar disorder Drugs used in Bipolar disorder Mood stabilisers Lithium Only specific anti-mania drug known Is drug of choice for treatment & prophylaxis of acute mania Carbamezepine, Sodium Valporate Antipsychotic drugs (may be used alone or in combination with BDZ) Note: Haloperidol, Zuclopenthixol, Olanzepine and Quetiapine approved for use in acute mania If patients unresponsive to drug treatment – electroconvulsive therapy may be useful Lithium – adverse effects Common Metallic taste Diarrhoea Epigastric discomfort Polyuria Weight gain Oedema Skin reactions e.g. acne Hypothyroidism Infrequent Nephrogenic diabetes insipidus with polydipsia and polyuria Rare Hyperthyroidism Lithium - Overdose Warning symptoms of lithium intoxication include; Extreme thirst, frequent urination, nausea and vomiting  anorexia Diarrhoea Drowsiness Ataxia Tinnitus Blurred vision Dysarthria Course tremor Treatment Not specific antidote for lithium poising Lithium treatment should be stopped and steps taken to reverse toxicity Serum levels monitored Lithium Cause of high blood levels Excessive dosage  lithium excretion  Sodium  Sodium loss – vomiting, diarrhoea, fever, Thiazide diuretics (e.g. chlorothiazide, hydrochlorothiazide) Dehydration Drug Interactions Blood levels or lithium are increased by; Thiazide diuretics, anti-inflammatory drugs and ACE inhibitors Blood levels are decreased by; Sodium salts (e.g. Sodium bicarbonate – found in indigestion medications e.g. Salvital, ural, citravescent) Hypnotics and Sedatives Hypnotics and Sedatives Medications to treat insomnia and anxiety Difficulty falling asleep or in staying asleep or disturbed sleep patterns → insufficient sleep Drug used to treat insomnia Hypnotics Anxiety may be due to A physical disorder (e.g. hyperthyroidism) or Use of legal or illicit drugs (e.g. corticosteroids, cocaine) Drugs used to treat symptoms of anxiety Anxiolytics (or sedatives) Sedatives & Hypnotics Examples Benzodiazepines Zolpidem Zopiclone Chloral hydrate Ethanol Barbiturates Sedationis a side effect of may drugs that are not general CNS depressants: Classical antipsychotics Antihistamines Gamma-Aminobutyric Acid (GABA) GABA is main inhibitory transmitter in brain Occurs fairly uniformly throughout brain tissue (very little in the peripheral tissues) Formed from glutamate by the enzyme glutamic acid decarboxylase (GAD) This enzyme is found only in GABA-synthesising neurons http://what-when-how.com/molecular-biology/gamma-aminobutyric-acid-gaba-molecular-biology/ Gamma-Aminobutyric Acid (GABA) Action of GABA is terminated mainly by uptake into the nerve terminals but also by deamination By GABA-transaminase (inhibited by Vigabatrin which is used in epilepsy) GABAA receptors are the target of a number of important centrally acting drugs including Benzodiazepine Barbiturate http://what-when-how.com/molecular-biology/gamma-aminobutyric-acid-gaba-molecular-biology/ Benzodiazepine – Mode of action Benzodiazepines Promote the binding of major inhibitory neurotransmitter GABA in the GABAA subtype of GABA receptors Bind with high affinity to an accessory site (Benzodiazepine BNZ receptor) on the GABAA receptor in such a way that they Promote the binding of GABA & Enhanced the GABA-induced ionic currents through the chloride channels http://www.arnoldgroup.org/Research-GABA%20Receptor.html Benzodiazepine – Mode of action Benzodiazepines appear to  the efficiency of GABA minergic synaptic inhibition by facilitating the frequency of opening of GABA-activated chloride ion channels Results in a  in the firing rate of critically important neurons in may regions of the brain. Benzodiazepines do not substitute for GABA i.e. they are not GABA-receptor agonist http://www.arnoldgroup.org/Research-GABA%20Receptor.html Benzodiazepines Indications Anxiety Insomnia Panic disorders Acute behavioural disturbance Seizures Muscle spasms Acute alcohol, barbiturate and benzodiazepine withdrawal Sedation procedures Comparative information Benzodiazepines can be categorised into different groups Very short acting (HL< 6 hours) Medium acting (12-24 hours) Midazolam (Hypnoval®)  Bromazepam (Lexotan®) Triazolam (Halcion®)  Lorazepam (Ativan®) Short acting (HL 6-12 hours) Long acting (HL > 24 hours) Alprazolam (Xanax®)  Clobazapam (Frisium®) Oxazepam (Murelax®,  Cloanazepam (Paxam®, Serepax®) Ribotril®) Temazepam (Normison®,  Diazepam (Valium®) Temaze®)  Flunitrazepam (Hypondorm®)  Nitrazepam (Aldorm®, Mogodon®) Benzodiazepines Withdrawal Symptoms Anxiety Insomnia Nightmares Irritability Dysphoria Sweating Hallucinations Tremors Tachycardia Hypertension Psychosis Seizures Benzodiazepines Withdrawal Symptoms Shorter acting BDZ are more likely to lead to acute withdrawal Symptoms High doses of BDZ used over a prolonged period can lead to more severe symptoms after discontinuation (agitation, depression, panic, & myalgia) Some symptoms May be similar to original complaint May continue for weeks/months BDZ best reserved for short term use 2 – 4 weeks Should be part of broader treatment plan Long term use can result in tolerance and dependence Drug seeking behaviour, craving etc. Drug interactions Additive CNS depression with drugs that act as CNS depressants; Alcohol Antihistamines Antidepressants Antipsychotics Opioid analgesics Benzodiazepine receptor antagonist In overdose BDZ → prolonged sleep, without serious depression of respiration or cardiovascular function When taken with other CNS depressants Can cause severe, sometimes life threatening respiratory depression Non-Benzodiazepine Anxiolytics Buspirone (Buspar®) Partial agonist at the 5HT1A receptor Indication - Anxiety Alternative where long term treatment is needed and BZD not desirable – less potential for dependence Concurrent use of BDZ  the efficacy of Buspirone Does not prevent BDZ withdrawal Optimal effect may take 2 weeks Common side effects – light headedness, dizziness, nausea, headaches, nervousness, excitement NOTE: Need to avoid grapefruit – may  risk side effects Non-Benzodiazepine Anxiolytics Zolpidem (Stilnox®) Indication – Short term treatment of insomnia Potentiates the inhibitory effect of GABA Is not a BDZ Adverse effects Common – diarrhoea Rare – paradoxical symptoms e.g. worsening insomnia, irritability, agitation Its Potential for tolerance, dependence or abuse is not clear Non-Benzodiazepine Anxiolytics Zopliclone (Imovane®, Imrest®) Indication – Short term treatment of insomnia Potentiates the inhibitory effect of GABA in the brain Adverse effects Common – taste disturbance (bitter), dry mouth Should be used short term Non-Benzodiazepine Anxiolytics Diphenhydramine (Snuzaid Gels®, Unisom®, Sleepgels®) Over the counter, 50mg nocte Injection of content of capsules (drug mis-users) may cause phelebitis, infection, more serious local effects Promathazine Doxylamine  Anticonvulsants (also known as antiepileptics) Anticonvulsants Anticonvulsants (Antiepileptic's) are used to control or prevent seizure disorders while minimising unwanted side-effects Aim for monotherapy (one medication) introduced slowly Trial and error (75% seizure free while 25% resistant) Desirable features highly effective with low toxicity long-acting and non-sedating not highly protein-bound inexpensive not resulting in tolerance Anticonvulsants Mechanism of action; Enhance GABA inhibition (e.g. benzodiazepines) or inhibit GABA transaminase (Vigabatrin, Tiagabine and Topiramate) Inhibit sodium channel function to stabilise the cell membrane (Phenytoin, Carbamazepine, Sodium Valproate and Lamotrigine) Inhibit calcium channel function or ‘calcium conductance’ (Ethosuximide) Raise brain levels of GABA (Gabapentin) Anticonvulsants Efficacy Different medications are more effective for treating specific seizures Anticonvulsants Side effects Behavioural and cognitive effects Anticonvulsants Other common side effects Depression of cardiovascular and respiratory system Enhance metabolism of Vitamin D – reduced bone mineral density Gastrointestinal effects Haematological effects Lithium NOTE: Long term use of lithium in therapeutic concentrations thought to cause histological and functional changes in kidney. Therefore should perform renal and thyroid function tests at baseline, then every 3-6 months Patient education Need to watch for signs of Lithium toxicity (e.g. extreme thirst and frequent urination, nausea and vomiting), especially during illness, excessive sweating or low fluid intake. If occurs – stop treatment STAT In general do not cease treatment abruptly – withdraw gradually to avoid relapse Take with food and consume more fluid (non-alcohol) during hot weather to avoid toxicity.