Psychiatry 5th year, 6th lecture (Dr. Saman Anwar)

Dr.Saman Anwar FarajPsychiatrist

M.B.Ch.B, F.I.B.M.S(PSYCH)

Drug treatment in psychiatry

The science of psychopharmacotherapy has expanded rapidly in the past decade, creating both an opportunity and a challenge.

Psychopharmacologic advances continue dramatically to expand the parameters of psychiatric treatments. Greater understanding of how the brain functions has led to more effective, less toxic, better-tolerated, and more specifically targeted therapeutic agents.

Principles of Psychopharmacotherapy

Principle 1 The diagnostic assessment, subject to revisions, is

fundamental to our model.Principle 2 Pharmacotherapy alone is generally insufficient for

complete recovery.Principle 3 The phase of an illness (e.g., acute, relapse,

recurrence) is of critical importance in terms of the specific intervention and the duration of treatment.

Principle 4 The risk-to-benefit ratio must always be considered

when developing a treatment strategy.

Principle 5 Prior personal (and possibly family) history of a good

or a poor response to a specific agent usually dictates the first-line choice for a subsequent episode.

Principle 6 It is important to target specific symptoms that serve

as markers for the underlying psychopathology and to monitor their presence or absence over an entire course of treatment.

Principle 7 It is necessary to observe for the development of

adverse effects throughout the entire course of treatment. Such monitoring often involves the use of the laboratory to ensure safety, as well as optimal efficacy.

antipsychoticsChlorpromazine (Thorazine), which was introduced in the

mid-1950s, was the first drug that significantly and consistently reduced symptoms of psychosis. Other drugs with similar clinical effects were introduced over the next two decades. Antipsychotic activity was related to high-affinity antagonism of dopamine D2 receptors. Accordingly, these agents are called dopamine receptor antagonists (DRAs). Other terms used to refer to these drugs are first-generation, typical, traditional, or conventional antipsychotics.

The DRAs are no longer the mainstay of the treatment of schizophrenia or other conditions associated with psychotic symptoms. Newer antipsychotic agents, the serotonin-dopamine antagonists (SDAs) and partial dopamine agonists (PDAs), also called second-generation, novel, or atypical antipsychotics, have largely replaced the DRAs as first-line treatments for the same spectrum of disorders. Not only do the newer agents cause fewer extrapyramidal side effects, but they may have greater effects against negative symptoms of schizophrenia, cognitive defects and depression that may coexist with psychosis

Indications for Antipsychotics The primary indication for this group of drugs is the presence

of psychosis in such disparate disorders as:1-Schizophrenia2-Schizophreniform disorder3-Schizoaffective disorder4-Delusional disorder5-Brief psychotic disorder6-Psychoses secondary to a nonpsychiatric medical condition7-Mood disorders with mood-congruent or incongruent psychotic

symptoms8-Mania9-Borderline personality disorder10-Substance-induced psychotic disorder11-Delirium and dementia12- Pervasive developmental disorder13-Tourette's syndrome14-Huntington's disease

Classical atypicalsChlorpromazine Promazine Triflupromazine ThioridazineStelazine

Trifluoperazine Fluphenazine ProchlorperazineLoxapine Haloperidol Droperidol

ClozapineRisperidoneOlanzapineQuetiapineZiprasidoneAripiprazole PimozideParliperidoneSertindoleZotepine

Side effectsA-dopamine blockage effects:

1-extrapyramidal side effects:i-acathisiaii-acute dystoniaiii-parkinsonian featuresiiii-tardive dyskinesia2-hyperprolactinemia3-neurolyptic malignant syndrome

Neuroleptic Malignant Syndrome

A potentially fatal side effect of DRA treatment, neuroleptic malignant syndrome, can occur at any time during the course of DRA treatment. Symptoms include extreme hyperthermia, severe muscular rigidity and dystonia, akinesia, mutism, confusion, agitation, and increased pulse rate and blood pressure (BP) leading to cardiovascular collapse. Laboratory findings include increased white blood cell (WBC) count, creatinine phosphokinase, liver enzymes, plasma myoglobin, and myoglobinuria, occasionally associated with renal failure. The symptoms usually evolve over 24 to 72 hours, and the untreated syndrome lasts 10 to 14 days. The diagnosis is often missed in the early stages, and the withdrawal or agitation may mistakenly be considered to reflect increased psychosis. Men are affected more frequently than are women, and young persons are affected more commonly than are elderly persons. The mortality rate can reach 20 percent to 30 percent or even higher when depot medications are involved. Rates are also increased when high doses of high-potency agents are used.

If neuroleptic malignant syndrome is suspected, the DRA should be stopped immediately and the following done: medical support to cool the person; monitoring of vital signs, electrolytes, fluid balance, and renal output; and symptomatic treatment of fever.

Antiparkinsonian medications may reduce some of the muscle rigidity. Dantrolene (Dantrium), a skeletal muscle relaxant may be useful in the treatment of this disorder. Once the person can take oral medications, dantrolene can be given in doses of 100 to 200 mg a day. Bromocriptine or amantadine can be added to the regimen. Treatment should usually be continued for 5 to 10 days.

B- acnticholinergic side effects: 1-blurred vision 2-urine retention 3-dry mouth 4-constipation 5-Some persons also have nausea and vomiting. 6-agitation© 7-halucination©

C- anti adrenergic side effects:1-reflex tachycardia2-postural hypotension3-ECG change4-sexual dysfunction5-arythmia (VT) and sudden death

D- anti histaminic and 5H1 blockade:1-sedation2-weight gain

E-Combined effects:Seizure Thresholdagitation; disorientation to time, person, and place;

hallucinationsA temporary leukopenia with a WBC count of about

3,500 is a common, but not serious problemAgranulocytosisThrombocytopenic or nonthrombocytopenic purpura,

hemolytic anemias, and pancytopenia may occur rarelyAllergic dermatitis and photosensitivity can occurUrticarial, maculopapular, petechial, and edematous

eruptions can occur early in treatment, generally in the first few weeks, and remit spontaneously(Persons should be warned of this adverse effect, spend no more than 30 to 60 minutes in the sun, and use sunscreens)

retinal pigmentationJaundiceElevations of liver enzymes

OverdosesOverdoses typically consist of exaggerated DRA side

effects. Symptoms and signs include central nervous system (CNS) depression, extrapyramidal symptoms, mydriasis, rigidity, restlessness, decreased deep tendon reflexes, tachycardia, and hypotension. The severe symptoms of overdose include delirium, coma, respiratory depression, and seizures. Haloperidol may be among the safest typical antipsychotics in overdose.

Activated charcoal, if possible, and gastric lavage should be administered if the overdose is recent. Emetics are not indicated, because the antiemetic actions of DRAs inhibit their efficacy. Seizures can be treated with IV diazepam (Valium) or phenytoin (Dilantin). Hypotension can be treated with either norepinephrine or dopamine, but not epinephrine.

AntidepressantsDepression is a common illness which affects a large

number of individuals in all societies. Over 10 per cent of the population will have a depression within their lifetime.

The primary treatment for depression involves the use of antidepressant drugs, and it is therefore important that clinicians become familiar with and adept in utilizing this important group of compounds. Although primarily used for the treatment of depression, drugs within this category also have a number of other important uses. A thorough understanding of the pharmacology of antidepressants will aid the clinician in the selective use of these drugs for patients with depression as well as patients with a number of other disorders.

AntidepressantsMAOI’sTCA’sSSRI’sSNRI’sOthers

TCA’sAmitryptilineClomipramineDothiepinImipramineLofepramineTrimipramine

TCA’s Pharmacodynamics1. Serotonine Uptake inhibitors2. Noradrenaline Uptake inhibitors3. Anticholinergic effect

constipation, dry mouth, blurred vision, drowsiness

4. Alpha-antagonistdizziness, low BP, drowsiness

5. Antihistamine actionwt. gain, drowsiness

SSRI’sCitalopram and EscitalopramFlouxetineFluvoxamineParoxetineSertraline

SNRI’sVenlefaxineDuloxetine

MAOISPhenelzineIsocarboxazidtranylcypromine

NRI’sReboxetine

OthersTrazodoneMertazapineMianserine

Toxic effects and overdose Often the most serious toxic effects are the result of overdose. Since

depressed patients are at increased risk of suicide there is always the possibility that suicidally depressed patients will overdose on their antidepressants. This is a very serious consideration and should be carefully evaluated when prescribing antidepressants. The symptoms and course of events following acute antidepressant overdose are complex and can be confusing unless a clear history of overdose is obtained. With tricyclic antidepressants, restlessness and excitement are initially seen with possible myoclonis, and dystonia and seizures leading to the development of coma. Seriously compromised patients can have depressed respiration with hypoxia, depressed reflexes, hypertension, and hypothermia. With the antidepressants that have antimuscarinic activity, there can be strong anticholinergic effects with mydriasis, flushed skin, dry membranes, and tachycardia.

Antidepressant overdose can be life-threatening and patients should receive immediate emergency medical evaluation. The local poison control centre should be contacted in any case of suspected antidepressant overdose. Appropriate follow-up can include the use of activated charcoal to absorb the drug as well as other medical supportive measures. Different compounds have different probability of serious complications following an overdose and this is related to the amount ingested. However, drugs are often taken in combination, and it is difficult to know the exact composition and amount of the overdose.

Mood StabilizersIndications for Mood Stabilizers

Bipolar IBipolar IICyclothymic disorderBipolar disorders not otherwise specified

(e.g., subsyndromal or subclinical mood disorders)

Adverse Effects of Lithium Neurologic

   Benign, nontoxic: dysphoria, lack of spontaneity, slowed reaction time, memory difficulties   Tremor: postural, occasional extrapyramidal   Toxic: coarse tremor, dysarthria, ataxia, neuromuscular irritability, seizures, coma, death   Miscellaneous: peripheral neuropathy, benign intracranial hypertension, myasthenia gravis-like syndrome, altered creativity, lowered seizure thresholdEndocrine   Thyroid: goiter, hypothyroidism, exophthalmos, hyperthyroidism (rare)   Parathyroid: hyperparathyroidism, adenomaCardiovascular   Benign T-wave changes, sinus node dysfunctionRenal   Concentrating defect, morphologic changes, polyuria (nephrogenic diabetes insipidus), reduced GFR, nephrotic syndrome, renal tubular acidosisDermatologic   Acne, hair loss, psoriasis, rashGastrointestinal   Appetite loss, nausea, vomiting, diarrheaMiscellaneous   Altered carbohydrate metabolism, weight gain, fluid retention

anxiolyticsBenzodiazepines:ChlordiazepoxideDiazepamOxazepam ChlorazepateLorazepam Prazepam HalazepamAlprazolam

Precautions and Adverse Reactions

The most common adverse effect of benzodiazepines is drowsiness, which occurs in about 10 percent of all persons. Because of this adverse effect, persons should be advised to be careful while driving or using dangerous machinery when taking the drugs.

ataxia The most serious adverse effects of benzodiazepines occur

when other sedative substances, such as alcohol, are taken concurrently. These combinations can result in marked drowsiness, disinhibition, or even respiratory depression. Infrequently, benzodiazepine receptor agonists cause mild cognitive deficits.

anterograde amnesiaparadoxical increase in aggressionslurred speechHyporeflexiaappetite stimulant effect and may cause weight gain.Some data indicate that benzodiazepines are teratogenic;

therefore, their use during pregnancy is not advised.

Tolerance DependenceWithdrawal

Signs and Symptoms of Benzodiazepine WithdrawalAnxiety Tremor Irritability Depersonalization Insomnia Hyperesthesia Hyperacusis Myoclonus Nausea Delirium Difficulty concentrating Seizures

5-HT1A partial agonists

The first, buspirone, was licensed in many countries some years ago

anxiolytic activity without hypnotic, anticonvulsant, or muscle-relaxant properties. Buspirone is much less sedative than the benzodiazepines and causes little or no psychomotor or cognitive impairment,(39

) nor does it potentiate the effects of alcohol.Antipsychotic drugsAntidepressantsb-Adrenoceptor antagonistsPropranololAntihistaminesDiphenhydraminehydroxizine

Anticholinergic DrugsIn the clinical practice of psychiatry, the

anticholinergic drugs are primarily used to treat medication-induced movement disorders, particularly neuroleptic-induced parkinsonism, neuroleptic-induced acute dystonia, and medication-induced postural tremor.

BenztropineBiperidenEthopropazineOrphenadrineProcyclidine(Kemadrin)Trihexyphenidyl(artane)

Precautions and Adverse Reactions

The adverse effects of the anticholinergic drugs result from blockade of muscarinic acetylcholine receptors. Anticholinergic drugs should be used cautiously, if at all, by persons with prostatic hypertrophy, urinary retention, and narrow-angle glaucoma. The anticholinergics are occasionally used as drugs of abuse because of their mild mood-elevating properties, most notably, trihexyphenidyl.

The most serious adverse effect associated with anticholinergic toxicity is anticholinergic intoxication, which can be characterized by delirium, coma, seizures, agitation, hallucinations, severe hypotension, supraventricular tachycardia, and peripheral manifestations—flushing, mydriasis, dry skin, hyperthermia, and decreased bowel sounds. Treatment should begin with the immediate discontinuation of all anticholinergic drugs.

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