Monthly Archives: November 2017

Drugs Used in Nausea and Vertigo

Drugs Used in Nausea and Vertigo

Vomiting during pregnancy

Nausea in the first trimester of pregnancy is generally mild and does not require drug therapy. On rare occasions if vomiting is severe, short-term treatment with an antihistamine, such as promethazine, may be required. Metoclopramide may be considered as second-line treatments. If symptoms do not settle in 24 to 48 hours then specialist opinion should be sought. Hyperemesis gravidarum is a more serious condition, which requires intravenous fluid and electrolyte replacement and sometimes nutritional support. Supplementation with thiamine must be considered in order to reduce the risk of Wernicke’s encephalopathy.

For indication, dosage, contraindications and available brands refer to drugs acting on gastrointestinal tract.

Postoperative nausea and vomiting

The incidence of postoperative nausea and vomiting depends on many factors including the anaesthetic used, the type and duration of surgery, and the patient’s sex. The aim is to prevent postoperative nausea and vomiting from occurring. Drugs used include some phenothiazines (e.g. prochlorperazine), metoclopramide (but 10-mg dose has limited efficacy and higher parenteral doses associated with greater side-effects), 5HT3 antagonists, antihistamines (such as cyclizine), and dexamethasone. A combination of two antiemetic drugs acting at different sites may be needed in resistant postoperative nausea and vomiting. For indication, dosage, contraindications and available brands refer to drugs acting on gastrointestinal tract.

Motion sickness

Antiemetics should be given to prevent motion sickness rather than after nausea or vomiting develop. The most effective drug for the prevention of motion sickness is hyoscine. A transdermal hyoscine patch provides prolonged activity but it needs to be applied several hours before travelling. The sedating antihistamines are slightly less effective against motion sickness, but are generally better tolerated than hyoscine. If a sedative effect is desired promethazine is useful, but generally a slightly less sedating antihistamine such as cyclizine or cinnarizine is preferred. The 5HT3 antagonists, domperidone, metoclopramide, and the phenothiazines (except the antihistamine phenothiazine promethazine) are ineffective in motion sickness. For indication, dosage, contraindications and available brands refer to drugs acting on gastrointestinal tract.

Other vestibular disorders

Management of vestibular diseases is aimed at treating the underlying cause as well as treating symptoms of the balance disturbance and associated nausea and vomiting. Vertigo and nausea associated with Ménière’s disease and middle-ear surgery can be difficult to treat.Betahistine is an analogue of histamine and is claimed to reduce endolymphatic pressure by improving the microcirculation. Betahistine is licensed for vertigo, tinnitus, and hearing loss associated with Ménière’s disease.

Antihistamines

CINNARIZINE:

Indications: vestibular disorders, such as vertigo, tinnitus, nausea, and vomiting in Ménière’s disease; motion sickness.

Contraindications: prostatic hypertrophy, urinary retention, susceptibility to angle-closure glaucoma, and pyloroduodenal obstruction. Antihistamines should be used with caution in hepatic disease.

Dose and Administration: Vestibular disorders, 30 mg 3 times daily; child 5– 12 years 15 mg 3 times daily. Motion sickness, 30 mg 2 hours before travel then 15 mg every 8 hours during journey if necessary; child 5–12 years, 15 mg 2 hours before travel then 7.5 mg every 8 hours during journey if necessary.

PROMETHAZINE HYDROCHLORIDE:

Indications: nausea, vomiting, vertigo, labyrinthine disorders, and motion sickness.

Contraindications: prostatic hypertrophy, urinary retention, susceptibility to angle-closure glaucoma, and pyloroduodenal obstruction. Antihistamines should be used with caution in hepatic disease.

Dose and Administration: Motion sickness prevention, 20–25 mg at bedtime on night before travel, repeat following morning if necessary; child under 2 years not recommended, 2–5 years 5 mg at night and following morning if necessary, 5–10 years 10 mg at night and following morning if necessary.

Phenothiazines and related drugs

CHLORPROMAZINE HYDROCHLORIDE:

Indications: nausea and vomiting of terminal illness (where other drugs have failed or are not available).

Contraindications: Coma, Lactating Mother, Neuroleptic Malignant Syndrome, Severe Cardiovascular Disease, and Stupor.

Dose and Administration: By mouth, 10–25 mg every 4–6 hours; child 500 micrograms/kg every 4–6 hours (1–5 years max. 40 mg daily, 6–12 years max. 75 mg daily). By deep intramuscular injection initially 25 mg then 25– 50 mg every 3–4 hours until vomiting stops; child 500 micrograms/kg every 6–8 hours (1–5 years max. 40 mg daily, 6–12 years max. 75 mg daily).

Domperidone and metoclopramide

DOMPERIDONE:

Indications: nausea and vomiting, dyspepsia, gastro-oesophageal reflux. Contraindications: prolactinoma, hepatic impairment; where increased gastro­intestinal motility harmful; pregnancy.

Dose and Administration: By mouth, adult and child body-weight over 35 kg, 10–20 mg 3–4 times daily; max. 80 mg daily; child body-weight up to 35 kg (nausea and vomiting only), 250–500 micrograms/kg 3–4 times daily; max. 2.4 mg/kg daily. By rectum in suppositories, adult and child body-weight over 35 kg, 60 mg twice daily; child 15–35 kg (nausea and vomiting only), 30 mg twice daily; child body-weight under 15 kg, not recommended.

METOCLOPRAMIDE HYDROCHLORIDE:

Indications: adults, nausea and vomiting, particularly in gastro-intestinal disorders and treatment with cytotoxics or radiotherapy; migraine. Contraindications: gastro-intestinal obstruction, perforation or haemorrhage; 3–4 days after gastro-intestinal surgery; phaeochromocytoma; breast-feeding. Dose and Administration: By mouth or by intramuscular injection or by intravenous injection over 1–2 minutes, nausea and vomiting, 10 mg (5 mg in young adults 15–19 years under 60 kg) 3 times daily; child up to 1 year (up to 10 kg) 1 mg twice daily, 1–3 years (10–14 kg) 1 mg 2–3 times daily, 3–5 years (15–19 kg) 2 mg 2–3 times daily, 5–9 years (20–29 kg) 2.5 mg 3 times daily, 9–14 years (30 kg and over) 5 mg 3 times daily.

5HT antagonists

ONDANSETRON:

Indications: Prevention of Cancer Chemotherapy-Induced Nausea and Vomiting, Prevention of Post-Operative Nausea and Vomiting, Prevention of Radiation-Induced Nausea and Vomiting.

Contraindications: Severe Hepatic Disease, Extrapyramidal Disease.

Dose and Administration: Moderately emetogenic chemotherapy or radiotherapy, by mouth, 8 mg 1–2 hours before treatment or by rectum, 16 mg 1–2 hours before treatment or by intramuscular injection or slow intravenous injection, 8 mg immediately before treatment then by mouth, 8 mg every 12 hours for up to 5 days or by rectum, 16 mg daily for up to 5 days; child, by slow intravenous injection or by intravenous infusion over 15 minutes, 5 mg/m2 immediately before chemotherapy then 4 mg by mouth every 12 hours for up to 5 days. Severely emetogenic chemotherapy, by intramuscular injection or slow intravenous injection, 8 mg immediately before treatment, where necessary followed by 2 further doses of 8 mg at intervals of 2–4 hours (or followed by 1 mg/hour by continuous intravenous infusion for up to 24 hours) then by mouth, 8 mg every 12 hours for up to 5 days or by rectum, 16 mg daily for up to 5 days; alternatively, by intravenous infusion over at least 15 minutes, 32 mg immediately before treatment or by rectum, 16 mg 1–2 hours before treatment then by mouth, 8 mg every 12 hours for up to 5 days or by rectum, 16 mg daily for up to 5 days; child, by slow intravenous injection, 5 mg/m2 immediately before chemotherapy then 4 mg by mouth every 12 hours for up to 5 days.

Other drugs for Ménière’s disease

BETAHISTINE DIHYDROCHLORIDE:

Indications: vertigo, tinnitus and hearing loss associated with Ménière’s disease.

Contraindications: phaeochromocytoma.

Dose and Administration: Initially 16 mg 3 times daily, preferably with food; maintenance 24–48 mg daily; child not recommended.

Drugs Used in the Treatment of Obesity

An anti-obesity drug should be considered only for those with a body mass index (BMI, individual’s body-weight divided by the square of the individual’s height) of 30 kg/m2 or greater in whom at least 3 months of managed care involving supervised diet, exercise and behaviour modification fails to achieve a realistic reduction in weight. In the presence of risk factors (such as diabetes, coronary heart disease, hypertension, and obstructive sleep apnoea), it may be appropriate to prescribe a drug to individuals with a BMI of 27 kg/m2 or greater, provided that such use is permitted by the drug’s marketing authorisation. Drugs should never be used as the sole element of treatment. The individual should be monitored on a regular basis; drug treatment should be discontinued if the individual regains weight at any time whilst receiving drug treatment. Combination therapy involving more than one anti-obesity drug is contra­indicated until further information about efficacy and long-term safety is available.

Anti-obesity drugs acting on the gastro­intestinal tract

Orlistat, a lipase inhibitor, reduces the absorption of dietary fat. It is used in conjunction with a mildly hypocaloric diet in individuals with a body mass index (BMI) of 30 kg/m2 or more or in individuals with a BMI of 28 kg/m2 in the presence of other risk factors such as type 2 diabetes, hypertension, or hypercholesterolaemia.

ORLISTAT:

Indications: adjunct in obesity.

Contraindications: chronic malabsorption syndrome; cholestasis; breast-feeding.

Dose and Administration: adult over 18 years, 120 mg taken immediately before, during, or up to 1 hour after each main meal (up to max. 360 mg daily); continue treatment beyond 12 weeks only if weight loss since start of treatment exceeds 5% (target for initial weight loss may be lower in patients with type 2 diabetes); child over 12 years, initiated by specialist only.

Other Antidepressant Drugs

Mirtazapine, a presynaptic alpha2-adrenoreceptor antagonist, increases central noradrenergic and serotonergic neurotransmission. It has few antimuscarinic effects, but causes sedation during initial treatment. Venlafaxine is a serotonin and noradrenaline re-uptake inhibitor (SNRI); it lacks the sedative and antimuscarinic effects of the tricyclic antidepressants. Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse.

MIRTAZAPINE:

Indications: major depression.

Contraindications: Manic Bipolar Disorder, Severe Chronic Neutropenia, And Suicidal Ideation.

Dose and Administration: Initially 15 mg daily at bedtime increased within 2–4 weeks according to response; max. 45 mg daily as a single dose at bedtime or in 2 divided doses; child and adolescent under 18 years not recommended.

VENLAFAXINE:

Indications: Depression, Generalized Anxiety Disorder, Neuropathic Pain, And Post Traumatic Stress Disorder, Social Phobia, Vasomotor Symptoms associated with Menopause.

Contraindications: Hypertension, Narrow Angle Glaucoma, Ocular Hypertension, Prolonged QT Interval, Recovery Phase Following Myocardial Infarct, Severe Uncontrolled Hypertension, Suicidal Ideation, Upper GI Bleed.

Dose and Administration: Depression, adult over 18 years, 75 mg daily as a single dose, increased if necessary after at least 2 weeks to 150 mg once daily; max. 225 mg once daily; child under 18 years not recommended. Generalised anxiety disorder, adult over 18 years, 75 mg daily as a single dose; discontinue if no response after 8 weeks. Social anxiety disorder, adult over 18 years, 75 mg daily as a single dose; discontinue if no response after 12 weeks.

TIANEPTINE:

Indications: Indicated for depressive states of mild, moderate and sever intensity.

Contraindications: Children under 15 years age, pregnancy, breast-feeding or not to be used in combination with other drugs for depression such as non­selective MAOI.

Dose and Administration: The mean dosage is 3 tablets per day (37.5mg per day) to be taken just before the three meals.

Tricyclic and related antidepressant drugs

Tricyclic and related antidepressants block the re-uptake of both serotonin and noradrenaline, although to different extents. Tricyclic and related antidepressants also show varying degrees of antimuscarinic side-effects and cardiotoxicity in overdosage, which may be important in individual patients. Evidence of the efficacy of tricyclic antidepressants for depression in children has not been established.

Tricyclic Antidepressant Drugs:

AMITRIPTYLINE HYDROCHLORIDE:

Indications: depressive illness, nocturnal enuresis in children, neuropathic pain and migraine prophylaxis.

Contraindications: Recovery Phase Following Myocardial Infarct, Alcoholism, Chronic Idiopathic Constipation, Conduction Disorder of the Heart, Congenital Long QT Syndrome, Epilepsy, Fainting, Hyperthyroidism, Manic Bipolar Disorder, Narrow Angle Glaucoma, Paralytic Ileus, Prolonged QT Interval, Suicidal Ideation, Torsades de Pointes, Urinary Retention.

Dose and Administration: Depression (but not recommended, see notes above), initially 75 mg (elderly and adolescents 30–75 mg) daily in divided doses or as a single dose at bedtime increased gradually as necessary to 150–200 mg; child under 16 years not recommended for depression. Nocturnal enuresis, child 7–10 years 10–20 mg, 11–16 years 25–50 mg at night; max. period of treatment (including gradual withdrawal) 3 months—full physical examination before further course. Neuropathic pain [unlicensed indication], initially 10–25 mg daily at night, increased if necessary to 75 mg daily; higher doses under specialist supervision. Migraine prophylaxis initially 10 mg at night, increased if necessary to maintenance of 50–75 mg at night.

CLOMIPRAMINE HYDROCHLORIDE:

Indications: Obsessive-Compulsive Disorder, Anxiety, Cataplexy Syndrome, Depression, and Panic Disorder.

ContraindicationsMalignant Hyperthermia, Recovery Phase Following Myocardial Infarct, Epilepsy, Glaucoma, Severe Renal Disease, And Suicidal Ideation.

Dose and AdministrationDepressive illness, initially 10 mg daily, increased gradually as necessary to 30–150 mg daily in divided doses or as a single dose at bedtime; max. 250 mg daily; elderly initially 10 mg daily increased carefully over approx. 10 days to 30–75 mg daily; child and adolescent under 18 years not recommended. Phobic and obsessional states, initially 25 mg daily (elderly 10 mg daily) increased over 2 weeks to 100–150 mg daily; max. 250 mg daily; child and adolescent under 18 years not recommended. Adjunctive treatment of cataplexy associated with narcolepsy, initially 10 mg daily, gradually increased until satisfactory response (range 10–75 mg daily); child and adolescent under 18 years not recommended.

IMIPRAMINE HYDROCHLORIDE:

Indications: Depression, Nocturnal Enuresis, Anxiety, Attention-Deficit Hyperactivity Disorder, Bulimia Nervosa, Cataplexy Syndrome, Narcolepsy Syndrome, Neuropathic Pain, Panic Disorder.

Contraindications: Malignant Hyperthermia, Recovery Phase Following Myocardial Infarct, Epilepsy, Glaucoma, Severe Renal Disease, And Suicidal Ideation.

Dose and Administration: Depression, initially up to 75 mg daily in divided doses increased gradually to 150–200 mg (up to 300 mg in hospital patients); up to 150 mg may be given as a single dose at bedtime; elderly initially 10 mg daily, increased gradually to 30–50 mg daily; child not recommended for depression. Nocturnal enuresis, child 7–8 years 25 mg, 8–11 years 25–50 mg, over 11 years 50–75 mg at bedtime; max. period of treatment (including gradual withdrawal) 3 months—full physical examination before further course.

MAPROTILINE:

Indications: Anxiety with Depression, Depression and Neuralgia.

Contraindications: Abnormal ECG, Epilepsy, Myocardial Infarction, Alcoholism, Bipolar Disorder, Blood Dyscrasias, Bronchial Asthma, Disease of Cardiovascular System, Disease of Liver, Glaucoma, Hyperthyroidism, Narrow Angle Glaucoma, Schizophrenia, Suicidal Ideation, Urinary Retention.

Dose and Administration: initially 25-75mg daily. Elderly initially 30mg as a single dose at bedtime daily or in 3 divided doses, increased as necessary to 150mg.

Related Antidepressant Drugs:

Tricyclic-related drugs have a lower incidence of antimuscarinic side-effects compared with older tricyclics. The tricyclic-related drugs may also be associated with a lower risk of cardiotoxicity in overdosage.

TRAZODONE HYDROCHLORIDE:

Indications: depressive illness, particularly where sedation is required; anxiety.

Contraindications: Myocardial Infarction, Non Q-Wave Myocardial Infarction, Priapism, Cardiac Disease, Conduction Disorder of the Heart, Suicidal Ideation.

Dose and Administration: Depression, initially 150 mg (elderly 100 mg) daily in divided doses after food or as a single dose at bedtime; may be increased to 300 mg daily; hospital patients up to max. 600 mg daily in divided doses; child not recommended. Anxiety, 75 mg daily, increasing if necessary to 300 mg daily; child not recommended.​

Antimanic Drugs

Drugs are used in mania to control acute attacks and to prevent their recurrence.

Benzodiazepines: Use of benzodiazepines may be helpful in the initial stages of treatment until lithium achieves its full effect; they should not be used for long periods because of the risk of dependence.

Antipsychotic drugs:

In an acute attack of mania, treatment with an antipsychotic drug is usually required because it may take a few days for lithium to exert its antimanic effect.

Carbamazepine:

Carbamazepine may be used for the prophylaxis of bipolar disorder (manic-depressive disorder) in patients unresponsive to lithium; it seems to be particularly effective in patients with rapid-cycling manic-depressive illness (4 or more affective episodes per year).

Valproic acid:

Valproic acid is licensed for the treatment of manic episodes associated with bipolar disorder. It may be useful in patients unresponsive to lithium.

LITHIUM DERIVATIVES:

Indications: Bipolar Disorder, Bipolar Disorder in Remission, Manic Bipolar Disorder.

Contraindications: Lactating Mother, Lithium Toxicity, Pregnancy, Chronic Heart Failure, Conduction Disorder of the Heart, Diabetes Insipidus, Hyponatremia, Renal Disease, Severe Dehydration, Severe Infection.

Dose and Administration: For lithium carbonate adult and child over 12 years, treatment, initially 1–1.5 g daily; prophylaxis, initially 300–400 mg daily. For lithium sulphate, Treatment and prophylaxis, initially 1.04–3.12 g daily in 2 divided doses (elderly or patients less than 50 kg, 520 mg twice daily).​

Antidepressant Drugs

Antidepressant drugs are effective for treating moderate to severe depression associated with psychomotor and physiological changes such as loss of appetite and sleep disturbance; improvement in sleep is usually the first benefit of therapy. They are also effective for dysthymia (lower grade chronic depression). Antidepressant drugs are not generally effective in mild depression, and cognitive behavioral therapy should be considered initially; however, a trial of antidepressant therapy may be considered in cases refractory to psychological treatments or those associated with psychosocial or medical problems. Drug treatment of mild depression may also be considered in patients with a history of moderate or severe depression. There is little to choose between the different classes of antidepressants in terms of efficacy, so choice should be based on the individual patient’s requirements, including the presence of concomitant disease, existing therapy, suicide risk, and previous response to antidepressant therapy. Since there may be an interval of 2 weeks before the antidepressant action takes place, electroconvulsive treatment may be required in severe depression when delay is hazardous or intolerable. Patients should be reviewed every 1–2 weeks at the start of antidepressant treatment. Treatment should be continued for at least 4 weeks (6 weeks in the elderly) before considering whether to switch antidepressant due to lack of efficacy. In cases of partial response, continue for a further 2 weeks (elderly patients may take longer to respond). Following remission, antidepressant treatment should be continued at the same dose for at least 6 months (about 12 months in the elderly). Patients with a history of recurrent depression should continue to receive maintenance treatment for at least 2 years.​

Antipsychotic Depot Injection

Long-acting depot injections are used for maintenance therapy especially when compliance with oral treatment is unreliable. However, depot injections of conventional antipsychotics may give rise to a higher incidence of extrapyramidal reactions than oral preparations; extrapyramidal reactions occur less frequently with atypical antipsychotics such as risperidone. Depot antipsychotics are administered by deep intramuscular injection at intervals of 1 to 4 weeks. When initiating therapy with sustained-release preparations of conventional antipsychotics, patients should first be given a small test-dose as undesirable side-effects are prolonged. In general not more than 2–3 mL of oily injection should be administered at any one site; correct injection technique (including the use of z-track technique) and rotation of injection sites are essential. If the dose needs to be reduced to alleviate side-effects, it is important to recognise that theplasma-drug concentration may not fall for some time after reducing the dose; therefore it may be a month or longer before side-effects subside. ​

 

FLUPENTHIXOL DECANOATE:

Indications: maintenance in schizophrenia and other psychoses.

Contraindications: hepatic impairment; renal impairment; pregnancy; breast-feeding.

Dose and Administration: By deep intramuscular injection into the gluteal muscle, test dose 20 mg, then after at least 7 days 20–40 mg repeated at intervals of 2–4 weeks, adjusted according to response; max. 400 mg weekly; usual maintenance dose 50 mg every 4 weeks to 300 mg every 2 weeks; elderly initially quarter to half adult dose; child not recommended.

 

RISPERIDONE:

Indications: Bipolar Disorder in Remission, Schizophrenia and other psychoses in patients tolerant to risperidone by mouth.

Contraindications: Akathisia, Constipation, Dizziness, Drowsy, Dyspepsia, Extrapyramidal Disease, Fatigue, Headache Disorder, Parkinsonism, Rhinitis, Weight Gain, Xerostomia.

Dose and Administration: By deep intramuscular injection into the gluteal muscle, patients taking oral risperidone up to 4 mg daily, initially 25 mg every 2 weeks; patients taking oral risperidone over 4 mg daily, initially 37.5 mg every 2 weeks; dose adjusted at intervals of at least 4 weeks in steps of 12.5 mg to max. 50 mg (elderly 25 mg) every 2 weeks; child and adolescent under 18 years not recommended.

 

ZUCLOPENTHIXOL DECANOATE:

Indications: maintenance in schizophrenia and other psychoses, particularly with aggression and agitation.

Contraindications: hepatic impairment; renal impairment; pregnancy; breast-feeding.

Dose and Administration: By deep intramuscular injection into the gluteal muscle, test dose 100 mg, followed after at least 7 days by 200–500 mg or more, repeated at intervals of 1–4 weeks, adjusted according to response; max. 600 mg weekly; elderly quarter to half usual starting dose; child not recommended. ​

Atypical Antipsychotics

The ‘atypical antipsychotics’ may be better tolerated than other antipsychotics; extrapyramidal symptoms may be less frequent than with older antipsychotics. the atypical antipsychotics should be considered when choosing first-line treatment of newly diagnosed schizophrenia. an atypical antipsychotic is considered the treatment option of choice for managing an acute schizophrenic episode when discussion with the individual is not possible. an atypical antipsychotic should be considered for an individual who is suffering unacceptable side-effects from a conventional antipsychotic. an atypical antipsychotic should be considered for an individual in relapse whose symptoms were previously inadequately controlled. changing to an atypical antipsychotic is not necessary if a conventional antipsychotic controls symptoms adequately and the individual does not suffer unacceptable side-effects.

 

AMISULPRIDE:

Indications: schizophrenia and other psychoses.

Contraindicationsthe possibility of cerebrovascular events should be considered carefully before treating any patient with a history of stroke or transient ischaemic attack; risk factors for cerebrovascular disease (e.g. hypertension, diabetes, smoking, and atrial fibrillation) should also be considered. also phaeochromocytoma, prolactin-dependent tumours; pregnancy and breast-feeding.

Dose and Administration: Acute psychotic episode, 400–800 mg daily in 2 divided doses, adjusted according to response; max. 1.2 g daily; child under 15 years not recommended. Predominantly negative symptoms, 50–300 mg daily; child under 15 years not recommended.

ARIPIPRAZOLE:

Indications: Bipolar Disorder in Remission, Depression Treatment Adjunct, Manic Bipolar Disorder, Mixed Bipolar I Disorder, and Schizophrenia.

Contraindications: Lactating Mother, Chronic Heart Failure, Metabolic Syndrome X, Neuroleptic Malignant Syndrome, Senile Dementia, Suicidal Ideation, Tardive Dyskinesia.

Dose and Administration: Schizophrenia, by mouth, adult over 18 years 10– 15 mg once daily, usual maintenance 15 mg once daily; max. 30 mg once daily. Mania, by mouth, adult over 18 years, 15 mg once daily, increased if necessary; max. 30 mg once daily.

 

CLOZAPINE:

Indications: Suicidal Behavior in Schizoaffective Disorder, Suicidal Behavior in Schizophrenia, Treatment-Resistant Schizophrenia, Bipolar Disorder in Remission, Manic Bipolar Disorder.

Contraindications: Agranulocytosis, Alcohol-Induced Psychosis, CNS Depression, Coma, Lactating Mother, Neoplastic Myeloproliferative Disorders, Neuroleptic Malignant Syndrome, Paralytic Ileus, Severe Neutropenic Disorder, Substance Overdose, Uncontrolled Epilepsy, Benign Prostatic Hypertrophy, Bladder Outflow Obstruction, Coronary Artery Disease, Deep Venous Thrombosis, Dehydration, Dilated Cardiomyopathy, Eosinophilia, Fainting, Hypotension, Hypovolemia, Leukopenia, Lower Abdominal Procedure, Lower Seizure Threshold, Metabolic Syndrome X, Myocarditis, Narrow Angle Glaucoma, Orthostatic Hypotension, Pulmonary Thromboembolism, Respiratory Depression, Seizure Disorder, Senile Dementia.

Dose and Administration: Schizophrenia, adult over 16 years, 12.5 mg once or twice (elderly 12.5 mg once) on first day then 25–50 mg (elderly 25–37.5 mg) on second day then increased gradually (if well tolerated) in steps of 25–50 mg daily (elderly max. increment 25 mg daily) over 14–21 days up to 300 mg daily in divided doses (larger dose at night, up to 200 mg daily may be taken as a single dose at bedtime); if necessary may be further increased in steps of 50–100 mg once (preferably) or twice weekly; usual dose 200–450 mg daily (max. 900 mg daily). Psychosis in Parkinson’s disease, adult over 16 years, 12.5 mg at bedtime then increased according to response in steps of 12.5 mg up to twice weekly; usual dose range 25–37.5 mg at bedtime, usual max. 50 mg daily; exceptionally, dose may be increased further in steps of 12.5 mg weekly to max. 100 mg daily in 1–2 divided doses.

 

OLANZAPINE:

Indications: Bipolar Disorder, Bipolar Disorder in Remission, Manic Bipolar Disorder, Mixed Bipolar I Disorder, and Schizophrenia.

Contraindications: Agranulocytosis, Breast Carcinoma, Cerebrovascular Accident, Cerebrovascular Disorder, Conduction Disorder of the Heart, Diabetes Mellitus, Heart Failure, Leukopenia, Metabolic Syndrome X, Myocardial Infarction, Myocardial Ischemia, Neuroleptic Malignant Syndrome, Neutropenic Disorder, Obesity, Paralytic Ileus, Senile Dementia, Suicidal Ideation, Transient Cerebral Ischemia.

Dose and Administration: Schizophrenia, combination therapy for mania, preventing recurrence in bipolar disorder, by mouth, adult over 18 years, 10 mg daily adjusted to usual range of 5–20 mg daily; doses greater than 10 mg daily only after reassessment; max. 20 mg daily. Monotherapy for mania, by mouth, adult over 18 years, 15 mg daily adjusted to usual range of 5–20 mg daily; doses greater than 15 mg only after reassessment; max. 20 mg daily. Control of agitation and disturbed behaviour in schizophrenia or mania, by intramuscular injection, adult over 18 years, initially 5–10 mg (usual dose 10 mg) as a single dose followed by 5–10 mg after 2 hours if necessary; elderly initially 2.5–5 mg as a single dose followed by 2.5–5 mg after 2 hours if necessary; max. 3 injections daily for 3 days; max. daily combined oral and parenteral dose 20 mg.

 

QUETIAPINE:

Indications: Bipolar Disorder, Bipolar Disorder in Remission, Depression associated with Manic Depressive Disorder, Manic Bipolar Disorder, Schizophrenia.

Contraindications: Constipation, Dizziness, Drowsy, Dyspepsia, Insomnia, Nasal Congestion, Orthostatic Hypotension, Weight Gain, and Xerostomia.

Dose and Administration: Schizophrenia, 25 mg twice daily on day 1, 50 mg twice daily on day 2, 100 mg twice daily on day 3, 150 mg twice daily on day 4, then adjusted according to response, usual range 300–450 mg daily in 2 divided doses; max. 750 mg daily; elderly initially 25 mg daily as a single dose, increased in steps of 25–50 mg daily in 2 divided doses. Mania, 50 mg twice daily on day 1, 100 mg twice daily on day 2, 150 mg twice daily on day 3, 200 mg twice daily on day 4, then adjusted according to response in steps of up to 200 mg daily to max. 800 mg daily; usual range 400–800 mg daily in 2 divided doses; elderly initially 25 mg daily as a single dose, increased in steps of 25–50 mg daily in 2 divided doses; child under 18 years, not recommended.

 

RISPERIDONE:

Indications: Infantile Autism, Manic Bipolar Disorder, Mixed Bipolar I Disorder, and Schizophrenia.

Contraindications: Lactating Mother, Neuroleptic Malignant Syndrome, Agranulocytosis, Breast Carcinoma, Cerebrovascular Disorder, Chronic Heart Failure, Conduction Disorder of the Heart, Dehydration, Diabetes Mellitus, Diffuse Lewy Body Disease, Disease of Cardiovascular System, Hypotension, Hypovolemia, Leukopenia, Metabolic Syndrome X, Myocardial Infarction, Neutropenic Disorder, Parkinsonism, Predisposed to Torsades de Pointes Cardiac Arrhythmias, Senile Dementia, Severe Renal Disease, Tardive Dyskinesia.

Dose and Administration: Psychoses, 2 mg in 1–2 divided doses on first day then 4 mg in 1–2 divided doses on second day (slower titration appropriate in some patients); usual dose range 4–6 mg daily; doses above 10 mg daily only if benefit considered to outweigh risk (max. 16 mg daily); elderly initially 500 micrograms twice daily increased in steps of 500 micrograms twice daily to 1– 2 mg twice daily. Mania, initially 2 mg once daily, increased if necessary in steps of 1 mg daily; usual dose range 1–6 mg daily; elderly initially 500 micrograms twice daily increased in steps of 500 micrograms twice daily to 1–2 mg twice daily.​

Drugs used in Psychosis and related disorders

When prescribing an antipsychotic for administration on an emergency basis, the intramuscular dose should be lower than the corresponding oral dose (owing to absence of first-pass effect), particularly if the patient is very active (increased blood flow to muscle considerably increases the rate of absorption). The prescription should specify the dose for each route and should not imply that the same dose can be given by mouth or by intramuscular injection. The dose of antipsychotic for emergency use should be reviewed at least daily.

Antipsychotic drugs

Antipsychotic drugs generally tranquillise without impairing consciousness and without causing paradoxical excitement but they should not be regarded merely as tranquillisers. For conditions such as schizophrenia the tranquillising effect is of secondary importance. In the short term they are used to quieten disturbed patients whatever the underlying psychopathology, which may be schizophrenia, brain damage, mania, toxic delirium, or agitated depression. Antipsychotic drugs are used to alleviate severe anxiety but this too should be a short-term measure. Selection is influenced by the degree of sedation required and the patient’s susceptibility to extrapyramidal side-effects. However, the differences between antipsychotic drugs are less important than the great variability in patient response; moreover, tolerance to secondary effects such as sedation usually develops. The atypical antipsychotics may be appropriate if extrapyramidal side-effects are a particular concern. Prescribing of more than one antipsychotic at the same time is not recommended; it may constitute a hazard and there is no significant evidence that side-effects are minimised.

CHLORPROMAZINE HYDROCHLORIDE:

Indications: Acute Intermittent Porphyria, Intractable Hiccups, Manic Bipolar Disorder, Nausea and Vomiting, Pre-Op Apprehension, Schizophrenia.

Contraindications: Coma, Lactating Mother, Neuroleptic Malignant Syndrome, Severe Cardiovascular Disease, Stupor, Breast Carcinoma, Conduction Disorder of the Heart, Congenital Long QT Syndrome, Disease of Liver, Extrapyramidal Disease, Glaucoma, Metabolic Syndrome X, Myocardial Infarction, Myocardial Ischemia, Obesity, Organophosphate Insecticide Poisoning, Prolonged QT Interval, Senile Dementia, Symptomatic Prostatic Hypertrophy, Tardive Dyskinesia, Torsades de Pointes, Urinary Retention

Dose and Administration: By mouth, schizophrenia and other psychoses, mania, short-term adjunctive management of severe anxiety, psychomotor agitation, excitement, and violent or dangerously  impulsive behaviour initially 25 mg 3 times daily (or 75 mg at night), adjusted according to response, to usual maintenance dose of 75–300 mg daily (but up to 1 g daily may be required in psychoses); elderly (or debilitated) third to half adult dose; child (childhood schizophrenia and autism) 1–5 years 500 micrograms/kg every 4–6 hours (max. 40 mg daily); 6–12 years 10 mg 3 times daily (max. 75 mg daily). By deep intramuscular injection, (for relief of acute symptoms but see also Cautions and Side-effects), 25–50 mg every 6–8 hours; child, 1–5 years 500 micrograms/kg every 6–8 hours (max. 40 mg daily); 6–12 years 500 micrograms/kg every 6–8 hours (max. 75 mg daily). Induction of hypothermia (to prevent shivering), 25– 50 mg every 6–8 hours; child 1–12 years, initially 0.5–1 mg/kg, followed by maintenance 500 micrograms/kg every 4–6 hours.

FLUPENTHIXOL:

Indications: schizophrenia and other psychoses, particularly with apathy and withdrawal but not mania or psychomotor hyperactivity; depression.

Contraindications: hepatic impairment; renal impairment; pregnancy; breast-feeding.

Dose and Administration: Psychosis, initially 3–9 mg twice daily adjusted according to the response; max. 18 mg daily; elderly (or debilitated) initially quarter to half adult dose; child not recommended.

HALOPERIDOL:

Indications: Acute Schizophrenia, Aggressive Behavior, Chronic Schizophrenia, Drug-Induced Psychosis, Gilles De La Tourette Syndrome, Manic Disorder, Organic Psychotic Condition, Psychotic Disorder, Schizophrenia

Contraindications: CNS Depression, Coma, Drug Induced CNS Depression, Lactating Mother, Parkinsonism, Torsades de Pointes, Agranulocytosis, Angina, Congenital Long QT Syndrome, Hypokalemia, Hypomagnesemia, Neuroleptic Malignant Syndrome.

Dose and Administration: schizophrenia and other psychoses, mania, short-term adjunctive management of psychomotor agitation, excitement, and violent or dangerously impulsive behaviour, by mouth, initially 1.5–3 mg 2–3 times daily or 3–5 mg 2–3 times daily in severely affected or resistant patients; in resistant schizophrenia up to 30 mg daily may be needed; adjusted according to response to lowest effective maintenance dose (as low as 5–10 mg daily); elderly (or debilitated) initially half adult dose; child initially 25–50 micrograms/kg daily (in 2 divided doses) to max. 10 mg. By intramuscular or by intravenous injection, initially 2–10 mg, then every 4–8 hours according to response to total max. 18 mg daily; severely disturbed patients may require initial dose of up to 18 mg; elderly (or debilitated) initially half adult dose; child not recommended. Agitation and restlessness in the elderly, by mouth, initially 0.5–1.5 mg once or twice daily.

SULPIRIDE:

Indications: schizophrenia and other psychoses.

Contraindications: hepatic impairment, renal impairment, cardiovascular disease, Parkinson’s disease (may be exacerbated by antipsychotics), epilepsy (and conditions predisposing to epilepsy), depression, myasthenia gravis, prostatic hypertrophy, or a susceptibility to angle-closure glaucoma

Dose and Administration: 200–400 mg twice daily; max. 800 mg daily in predominantly negative symptoms, and 2.4 g daily in mainly positive symptoms; elderly, lower initial dose, increased gradually according to response; child under 14 years not recommended.

TIAPRIDE:

Indications: Treatment of certain beha-vioural disorders and for the treatment of certain types of intense and referactory pains.

Contraindications: prolactin dependent tumor, pheochromocytoma.

Dose and Administration: dosage is variable and has to be adjusted to each individual case. For use in adults and children over the age of 6 years only.

ZUCLOPENTHIXOL ACETATE:

Indications: short-term management of acute psychosis, mania, or exacerbations of chronic psychosis

Contraindications: hepatic impairment; renal impairment; pregnancy; breast-feeding.

Dose and Administration: By deep intramuscular injection into the gluteal muscle or lateral thigh, 50–150 mg (elderly 50–100 mg), if necessary repeated after 2–3 days (1 additional dose may be needed 1–2 days after the first injection); max. cumulative dose 400 mg per course and max. 4 injections; max. duration of treatment 2 weeks—if maintenance treatment necessary change to an oral antipsychotic 2–3 days after last injection, or to a longer acting antipsychotic depot injection given concomitantly with last injection of zuclopenthixol acetate; child not recommended

ZUCLOPENTHIXOL:

Indications: schizophrenia and other psychoses, particularly when associated with agitated, aggressive, or hostile behaviour

Contraindications: hepatic impairment; renal impairment; pregnancy; breast-feeding and apathetic or withdrawn states.

Dose and Administration: By mouth, initially 20–30 mg daily in divided doses, increasing to a max. of 150 mg daily if necessary; usual maintenance dose 20– 50 mg daily; elderly (or debilitated) initially quarter to half adult dose; child not recommended​

Hypnotics and anxiolytics

Most anxiolytics (sedatives) will induce sleep when given at night and most hypnotics will sedate when given during the day. Prescribing of these drugs is widespread but dependence (both physical and psychological) and tolerance occurs. This may lead to difficulty in withdrawing the drug after the patient has been taking it regularly for more than a few weeks. Hypnotics and anxiolytics should, therefore, be reserved for short courses to alleviate acute conditions after causal factors have been established. Benzodiazepines are the most commonly used anxiolytics and hypnotics; they act at benzodiazepine receptors which are associated with gamma-aminobutyric acid (GABA) receptors. Older drugs such as meprobamate and barbiturates are not recommended—they have more side-effects and interactions than benzodiazepines and are much more dangerous in overdosage.

Hypnotics

Before a hypnotic is prescribed the cause of insomnia should be established and, where possible, underlying factors should be treated. However, it should be noted that some patients have unrealistic sleep expectations, and others understate their alcohol consumption which is often the cause of insomnia.

Chloral Hydrate:

Indications: General Anesthesia Adjunct, Insomnia, and Sedation in Pediatric Patients.

Contraindications: Esophagitis, Gastritis, Peptic Ulcer, Severe Hepatic Disease, Severe Renal Disease, Acute Intermittent Porphyria, Severe Cardiovascular Disease, Substance Abuse

Dose and Administration: chloral hydrate 200 mg/5mL (4%) in a suitable vehicle with a black currant flavor. Child 1 month–1 year 30–50 mg/kg, taken well diluted with water at bedtime. 1–12 years 30–50 mg/kg (max. 1 g), taken well diluted with water at bedtime.

Anxiolytics

Benzodiazepine anxiolytics can be effective in alleviating anxiety states. Although these drugs are often prescribed to almost anyone with stress-related symptoms, unhappiness, or minor physical disease, their use in many situations is unjustified. In particular, they are not appropriate for treating depression or chronic psychosis. In bereavement, the psychological adjustment may be inhibited

by benzodiazepines. In children, anxiolytic treatment should be used only to relieve acute anxiety (and related insomnia) caused by fear (e.g. before surgery). Anxiolytic treatment should be limited to the lowest possible dose for the shortest possible time. Dependence is particularly likely in patients with a history of alcohol or drug abuse and in patients with marked personality disorders.

Benzodiazepines

Benzodiazepines are indicated for the short-term relief of severe anxiety but long-term use should be avoided. In panic disorders (with or without agoraphobia) resistant to antidepressant therapy may be used; alternatively, a benzodiazepine may be used as short-term adjunctive therapy at the start of antidepressant treatment to prevent the initial worsening of symptoms.

DIAZEPAM:

Indications: short-term use of anxiety or insomnia, the adjunct to acute alcohol withdrawal; status epilepticus, febrile convulsions, muscle spasm, peri-operative use.

Contraindications: Lactating Mother, Myasthenia Gravis, Narrow Angle Glaucoma, Pregnancy, Respiratory Depression, Severe Hepatic Disease, Sleep Apnea, Alcohol Intoxication, Depression, Pulmonary Disease, Severe Chronic Obstructive Pulmonary Disease.

Dose and Administration: By mouth, anxiety, 2 mg 3 time’s daily increased if necessary to 15–30 mg daily in divided doses; elderly (or debilitated) half adult dose. Insomnia associated with anxiety, 5–15 mg at bedtime. By intramuscular injection or slow intravenous injection (into a large vein, at a rate of not more than 5 mg/minute), for severe acute anxiety, control of acute panic attacks, and acute alcohol withdrawal, 10 mg, repeated if necessary after not less than 4 hours

ALPRAZOLAM:

Indications: Anxiety, Anxiety with Depression, Generalized Anxiety Disorder, Panic Disorder and Insomnia.

Contraindications: Lactating Mother, Narrow Angle Glaucoma, Pregnancy, Alcohol Intoxication, CNS Depression, Depression, Fainting, Seizure Disorder, Sleep Apnea, Substance Abuse, Suicidal Ideation.

Dose and Administration: 250–500 micrograms 3 times daily (elderly or debilitated 250 micrograms 2–3 times daily), increased if necessary to a total of 3 mg daily; child not recommended.

LORAZEPAM:

Indications: short-term use of anxiety or insomnia, status epilepticus, and peri­operative

Contraindications: Alcohol Intoxication, Narrow Angle Glaucoma, Pregnancy, Respiratory Depression, Sleep Apnea, Depression, Fainting, Hepatic Encephalopathy, Severe Chronic Obstructive Pulmonary Disease, Severe Hepatic Disease.

Dose and Administration: By mouth, anxiety, 1–4 mg daily in divided doses; elderly (or debilitated) half adult dose.

BROMAZEPAM:

Indications:  used to relieve anxiety, nervousness, and tension.

Contraindications: Lactating Mother, Narrow Angle Glaucoma, Pregnancy, Alcohol Intoxication, CNS Depression, Depression, Fainting, Seizure Disorder, Sleep Apnea, Substance Abuse, Suicidal Ideation.

Dose and Administration: By mouth, anxiety, 6-18 mg daily in divided doses; elderly (or debilitated) half adult dose.

 

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