Psychopharmacology

Prasanta Kumar Roy

Since the late 1940s that drug treatment has been able to play a useful role in the management of psychiatric disorders Drug treatment now plays in indisputable role in management of severe psychiatric disorder

History of Drug Treatment in Psychiatry

Opiates and anticholinergic agents, have been used in the treatment of mental disorders for hundreds of years The first drug that was discovered to have a specific effect on a prticular psychiatric disorder was lithium (1949)

Introduction of some drug treatments in psychiatry

1949 Lithium 1952 Chlorpromazine 1954 Benzodiazepines 1957 Iproniazid (MAOI) 1957 Imipramine 1971 Carbamazepine 1980 Selective serotonin reuptake inhibitors 1988 Clozapine for treatment-resistant schizophrenia

PHARMACOLOGICAL ACTIONS

Pharmacokinetics is the study of how the body handles a drug Pharmacodynamics is the study of the effects of the drug on the body Pharmacokinetic drug interactions are the effects of drugs on the plasma concentrations of each other Pharmacodynamic drug interactions are the effects of drugs on the biological activities of each other

Pharmacokinetics
(How drug reaches to site of action)

Need to reach the brain in adequate amounts This depends on how well they are absorbed from the gastrointestinal tract into the blood stream Subsequently, drugs are broken down or metabolized in the liver and then eliminated from the body in the urine by the kidney

Plasma concentrations of drugs throughout the day vary, rising immediately after each dose and falling at a rate that differs between individual drugs and to some extent between individual people. Rate of decline influences how long the drug persists in the body Plasma half-life: the time taken for its concentration to fall by a half, once dosing has ceased

With most psychotropic drugs, the amount eliminated over time is proportional to plasma concentration it will take approximately five times the half-life for the drug to be eliminated from plasma when dosing with a drug begins, it will take five times the half-life for the concentration in plasma to reach a steady state. Most psychotropic drugs have fairly long halflives and once or twice daily dosing is sufficient

Pharmacodynamics
(How it works after it reaches to site)

Major pharmacodynamic considerations include : receptor mechanisms; the dose-response curve; the therapeutic index; the development of tolerance, dependence, and withdrawal phenomena.

A drug can be: An agonist for a receptor, thus stimulating the specific biological activity of the receptor; An antagonist, thus inhibiting the biological activity. The receptor site for a psychopharmacological drug is often the receptor for an endogenous neurotransmitter.

Classification
Class of drug Examples of classes

Antipsychotic

Phenothiazines,Butyrophenones Dibenzazepine

Antidepressant Mood stabilizer Anxiolytic Hypnotic

TCA, MAOIs, SSRIs, SNRIs Lithium, Carbamazepine, Valproate Benzodiazepines, azapirones (buspirone)
Benzodiazepines, Cyclopyrrolones, imidazopyridine

Mental Disorder
Alcohol use disorders

Common Drugs
-adrenergic receptor antagonists Benzodiazepines Carbamazepine Disulfiram Lithium Naltrexone

Bipolar I disorder Cyclothymic disorder

Anticonvulsants Benzodiazepines (especially clonazepam) Calcium channel inhibitors Dopamine receptor antagonists Lithium Serotonin-dopamine antagonists l-tryptophan

Mental Disorder Depressive disorders Dysthymia

Common Drugs
Anticonvulsants Benzodiazepines (especially alprazolam) Bromocriptine Bupropion Calcium channel inhibitors Lithium Mirtazapine Monoamine oxidase inhibitors Nefazodone Reboxetine Serotonin-noradrenaline reuptake inhibitors Selective serotonin reuptake inhibitors Sympathomimetics Thyroid hormones Trazodone Tricyclic and tetracyclic drugs l-Tryptophan

Mental Disorder Eating disorders

Common Drugs
Lithium MAOIs SSRI Trazodone Tricyclics and tetracyclics

Generalized anxiety disorder

-adrenergic receptor antagonists Barbiturates Benzodiazepines Buspirone SNRI SSRI Trazodone Tricyclics and tetracyclics

Mental Disorder Intermittent explosive disorder

Common Drugs
Anticonvulsants -adrenergic receptor antagonists Barbiturates (primarily for acute agitation) Buspirone Dopamine receptor antagonists Lithium Serotonin-dopamine antagonists

Obsessive-compulsive disorder PTSD (MAOIs)

SSRI Tricyclics and tetracyclics

Mental Disorder Opioid use disorders

Common Drugs
Clonidine Naltrexone Opioid agonists

Panic disorder Phobia

-adrenergic receptor antagonists Benzodiazepines (especially alprazolam and clonazepam) MAOIs SSRIs Tricyclics and tetracyclics

Mental Disorder Schizophrenia

Common Drugs
Anticonvulsants Benzodiazepines Dopamine receptor antagonists Lithium Serotonin-dopamine antagonists

Sexual dysfunctions

Antihistamines (cyproheptadine) Bupropion Sildenifil Sympathomimetics Yohimbine

Mental Disorder Sleep disorders

Common Drugs
Antihistamines Barbiturates and similarly acting drugs

Benzodiazepines Chloral hydrate Sympathomimetics Trazodone l-tryptophan

-Adrenergic Receptor Antagonists

Used to control hypertension, cardiac arrhythmias, hyperthyroidism, glaucoma, and tremor; for migraine prophylaxis Common antagonists are propranolol, nadolol, pindolol, labetalol, metoprolol, atenolol and acebutolol

Psychiatric Uses for -Adrenergic Receptor Antagonists

Definitely effective Performance anxiety Lithium-induced tremor Neuroleptic-induced akathisia Probably effective Adjunctive therapy for alcohol withdrawal and other substance-related disorders Adjunctive therapy for aggressive or violent behavior Possibly effective Antipsychotic augmentation Antidepressant augmentation

Side effects of -Adrenergic Receptor Antagonists

Cardiovascular: Hypotension, Bradycardia Respiratory: Asthma Gastrointestinal: Nausea, Diarrhea, Abdominal

pain

Sexual Function: Impotence Neuropsychiatric: Fatigue, Dysphoria,

Insomnia, Vivid nightmares

Anticonvulsants:
Carbamazepine
Was developed in the late 1950s Antiepileptic properties were first reported in 1963 Is used for: (1) partial seizures with complex symptomatology (psychomotor, temporal lobe, (2) generalized tonic-clonic seizure, and (3) mixed seizure patterns A second-line agent for mood disorder Impulse control & BPD

Anticonvulsants:
Carbamazepine

Contraindicated in bone marrow suppression, hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as amitriptyline or imipramine. Pt. who is taking MAOIs and pregnant female. Side Effects: Double or blurred vision, Vertigo, Gastrointestinal disturbances, Task performance impairment, Hematological effects, dizziness, sedation, skin rash

Anticonvulsants:
Valproate

Is used: (1) the treatment of the manic episodes associated with bipolar disorder; (2) sole and adjunctive therapy for CPS that occur either in isolation or in association with other types of seizures, sole and adjunctive therapy for SPS & CPS, and adjunctive therapy for multiple seizure that includes absence seizures; and (3) the prophylaxis of migraine headaches. some chronic pain and movement disorders as well as depressive, schizoaffective, anxiety, eating, alcohol use, substance use, impulse control, personality, and cognitive disorders.

Adverse effects of valproate

Common Gastrointestinal irritation Nausea Sedation Tremor Weight gain Hair loss Uncommon Vomiting Diarrhea Ataxia Dysarthria

Other Anticonvulsants

GABAPENTIN LAMOTRIGINE TOPIRAMATE

Lithium

Used at CIP in 1952 for the 1st time THERAPEUTIC INDICATIONS Bipolar Disorders At acute phase serum lithium level 1 or 1.2 mEq/L, 0.6 to 1.2 mEq/L as desirable for long-term control Maintenance Therapy Major Depressive Disorder, Schizoaffective Disorder, Aggression, Attention-deficit/hyperactivity disorder, Eating disorders, impulse-control disorders, Klein-Levin syndrome, Periodic catatonia, Periodic hypersomnia, Personality disorders, PMD, Sexual deviation

Lithium: Side effects

Neurological Reactions: Tremor, Lithium Intoxication, Thyroid Reactions: Clinical hypothyroidism, goiter, Cardiovascular Reactions: Benign, reversible Twave changes on the ECG, heart block Renal Reactions: Polyuria, alter kidney morphology Other Reactions: Weight gain, Gastrointestinal adverse effects, Dermatological adverse effects, Alterations in calcium metabolism, Sexual dysfunction,

Benzodiazepines

Benzodiazepines are anxiolytic, sedative, and in larger doses hypnotic Have muscle relaxant and anticonvulsant properties Benzodiazepines enhance GABA neurotransmission, thereby altering indirectly the activity of many other neurotransmitters, for example, noradrenaline and serotonin

Benzodiazepines

High potency benzodiazepines and those with short half-lives are more likely to be associated with dependence and withdrawal. Benzodiazepines with short half-lives (less than 12 hours) include lorazepam and temazepam. Because of problems with dependence, longacting compounds are preferable for the management of anxiety The long-acting benzodiazepines include drugs such as diazepam and chlordiazepoxide.

Therapeutic Indications of Benzodiazepines

Insomnia Seizures Alcohol Withdrawal Anxiety Disorders Depression To treat situational anxiety, especially that associated with medical treatment, and as muscle relaxants Catatonia

Side effects of Benzodiazepines

CNS (sedation, ataxia, amnestic) Behavioural disinhibition Sexual dysfunction Abuse Withdrawal symptom: Anxiety, Irritability, Insomnia, Fatigue, Headache, Muscle twitching or aching, Tremor, shakiness, Sweating, Dizziness, Concentration difficulties, Nausea, loss of appetite, Observable depression, Depersonalization, derealization, Increased sensory perception (smell, sight, taste, touch), Abnormal perception or sensation of movement

Dopamine Receptor Antagonist (Typical Antipsychotics)

The first antipsychotic drugs were the phenothiazines. In 1950 Paul Charpentier in Paris synthesized chlorpromazine In 1958 the first effective butyrophenone, haloperidol, was introduced by Paul Janssen from Belgium. First long-acting antipsychotic fluphenazine came in 1960

Typical Antipsychotics: Indications

Acute Psychosis Maintenance Therapy Mania Depression With Psychotic Symptoms Delusional Disorder Borderline Personality Disorder Substance-Induced Psychotic Disorder Delirium and Dementia Pervasive Developmental Disorders Impulse-Control Disorders Tourette's Disorder

Typical Antipsychotics: Side effects

Acute extrapyramidal syndromes Akathisia Acute dystonia Parkinsonism Neuroleptic malignant syndrome: (1) hyperthermia; (2) severe muscular rigidity; (3) autonomic instability including hyperthermia, tachycardia, increased blood pressure, tachypnea, and diaphoresis; and (4) changing levels of consciousness. Chronic extrapyramidal syndromes Tardive dyskinesia Perioral tremor (rabbit syndrome) Can induce electrocardiographic (ECG) abnormalities

Typical Antipsychotics: Side effects

Orthostatic (Postural) Hypotension Sudden Unexplained Death Anticholinergic effects include dry mouth, constipation, occasional diarrhea, and urinary retention Skin and Eye Effects Increase circulating prolactin concentrations in women, can lead to breast enlargement, galactorrhea, and irregular menses including infertility, or frank amenorrhea. Increased prolactin concentration associated with dopamine receptor antagonists may also suppress testosterone in men. Effects on Sexual Function lower the seizure threshold

Atypical antipsychotic
Having some activity against so-called negative symptoms of schizophrenia Clozapine is an important drug because it is the only drug with established efficacy in patients who are resistant to other antipsychotic treatments Side-effects: Sedation, hypotension and sexual dysfunction should be used cautiously in early pregnancy clozapine requires special monitoring with regard to blood white cell count

Mirtazapine
Noradrenergic and specific serotonergic antidepressants Indications: Major Depressive Disorder, Major Depressive Disorder With Sleep Disturbances, Major Depressive Disorder With Anxiety, Major Depressive Disorder With Cognitive Disturbances, Anxiety Disorders

Mirtazapine

Side-effects: somnolence, nausea, restless leg syndrome, dry mouth, increased appetite, and weight gain

Monoamine Oxidase Inhibitors

THERAPEUTIC INDICATIONS: drugs of choice for atypical depression and depression associated with anxiety, panic, and phobias; refractory thought disorders; narcoleptic states, migraine, narcolepsy, attention-deficit disorder Side Effects: tyramine-inducedhypertensive crisis, hypotension is a more common cardiovascular adverse effect, leading to dizziness and fainting

Selective Serotonin-Noradrenaline Reuptake Inhibitors

Venlafaxine, duloxetine Indications: Severe MDD, SSRI nonrespondent, elderly pt., Side-effects: chills, hypertension, anorexia, nausea, agitation, dizziness, somnolence, tremor, yawning, sweating, and abnormal ejaculation.

Selective Serotonin Reuptake Inhibitors

Fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine Indication: Depression, Seasonal Affective Disorder, Eating disorder, Panic, GAD, OCD, Trichotillomania, Social Phobia, Substance Dependence, PME, Unwanted effects : nausea, appetite loss, dry mouth, diarrhea, constipation, headache, insomnia, dizziness, anxiety, fatigue, tremor, somnolence, sweating, delayed orgasm, anorgasmia

Tricyclic Antidepressants
The first tricyclic to be introduced was imipramine. Amitriptyline, dothiepin, desipramine and nortriptyline Indications: Depression, panic disorder, chronic pain syndromes and migraine headache prophylaxis, Eneuria Side-effects: Anticholinergic : Dry mouth, tachycardia, blurred vision, glaucoma, constipation, urinary retention, cognitive impairment Antiadrenergic : Drowsiness, postural hypotension, sexual dysfunction Cardiac conduction defects, cardiac arrhythmias, epileptic seizures, Weight gain

Electroconvulsive Therapy

an important nonpharmacological intervention a substantial minority of patients do not respond to pharmacological treatment suffer severe adverse effects that make medications intolerable ECT offers a useful, safe, and, in some cases, lifesaving intervention

Electroconvulsive Therapy

ECT involves the passage of a brief electrical current through the brain to induce a generalized central nervous system (CNS) seizure under general anesthesia and muscle relaxation favorable response to ECT can occur quickly clinical benefits require multiple treatments administered over a period of several weeks

Electroconvulsive Therapy

generally well tolerated by patients can be used prophylactically to sustain a partial or complete remission of symptoms ECT is the most effective treatment available for hospitalized patients with major depression, and it is useful in the management of patients with mania, catatonia, schizophrenia, and certain neurological disorders

Electroconvulsive Therapy: History

The first use of convulsive therapy for the treatment of a psychiatric disorder by Ladislaus von Meduna in 1934 Hypothesizing a biological antagonism between seizures and psychosis, von Meduna used camphor injections to induce seizures In 1938, Luigi Bini and Ugo Cerletti documented the first therapeutic use of electrically induced seizures in humans.

Electroconvulsive Therapy: History

In 1940 A. E. Bennett introduced the use of curare as a muscle relaxant to avoid muscle contractions and minimize the risk of fractures. In 1943, CIP, Ranchi

repeated production of generalized CNS seizures is required to produce the clinical benefits of ECT Subconvulsive electrical stimuli or those inducing only partial (focal) seizures have no therapeutic benefit treatments in which seizures are terminated immediately following stimulation are ineffective

GENERAL PATIENT MANAGEMENT

Informed Consent Pre-ECT Evaluation Electrode Placement ECT Course

CONTRAINDICATIONS TO ECT

large CNS lesions, evidence of increased intracranial pressure, evidence of midline shift on neuroimaging studies, or neurological examinations that show clear focal deficits who have had neurosurgical procedures or who have had skull fractures recent myocardial infarction or stroke

ADVERSE EFFECTS AND RISKS

a period of increased parasympathetic tone produces profound bradycardia ECT is a medical procedure that involves general anesthesia. As a consequence it carries a small but definite risk of death. Cognitive Impairment Brain Damage Spontaneous Seizures Fracture, headache