Psychopharmacology

George Hsiao

2008

Therapeutic overview

“Writing prescription is easy, understanding people is hard.”

(Franz Kafka, 1883-1924)

The use of drugs with demonstrated efficacy in psychiatric disorder has become widespread since the mid-1950s.

Psychotropic agents:1) Antipsychotic (neuroleptic) drugs2) Antianxiety-sedative agents 3) Antidepressants (mood-elevating agents)4) Mood-stabilizing drugs

1.Psychosis (精神病 ) is a thought disorder characterized by disturbances of reality and perception, impaired cognitive function and inappropriate or diminished affect.

2. Two major of psychotic states are described as severe manic (躁症 ) or depressive (鬱症 ) illness schizophrenia (精神分裂症 ).

The use of drugs in treatment of psychiatric disorders is becoming more precise as psychiatric terminology and criteria for psychiatric disorders currently are well described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).

Vincent Van Gogh (Dutch Post-Impressionist Painter, 1853-

1890)

3. Symptoms of schizophrenia a) Positive symptoms: hallucination ( 幻覺 ), delusion ( 妄想 ), and

bizarre ( 古怪 ) or disorganized behavior. b) Negative symptoms: diminished speech, blunted emotions, loss of

energy and inability to experience pleasure (anhedonia, 乏樂症 ).

4. Schizophrenia is idiopathic (異質症 ) in nature.

Genetic factors, neurodevelopmental abnormalities, and environmental stressors are the possible etiological causes.

*Psychoanalysis (1900)……..Freud (major in neurotics Tx)

Electroconvulsive Therapy (ECT)

The Typical and Atypical Antipsychotic Drugs

1) Chlorpromazine and haloperidol have been the most widely utilized antipsychotics.

2) The efficacy of antipsychotics appears to dependent on the abilities to disrupt dopaminergic neurotransmission through the blockade of postsynaptic dopamine receptors (especially D2) or nerve depolarization blockade.

Henri Laborit (Paris, 1952) : chlorpromazine

Schizophrenia is associated with increased dopaminergic activity in the limbic structures of the brain. There is an increased number of dopamine-D2 receptor in the brain and there maybe overproduction of dopamine.

Dopaminergic receptor

Neurons Containing Dopamine

Dopamine

D2 receptor

Antagonist D2

Autoreceptor inactivation (depolarization Blockade)

3) Atypical antipsychotic drug, clozapine, selectively affects dopaminergic neurons of mesolimbic and mesocortical pathways. It exhibits a high affinity for D4 receptors as well as for several subtypes of the serotonin receptor, but a low affinity for D2.

4) The new atypical antipsychotic drugs (e.g. risperidone, olanzepine and sertindole) are similar to that of clozapine in terms of efficacy.

Neurons Containing 5-HT Form a Chain of Raphe Nuclei

Serotonin transmission

Localisation of function (via some transmitters) within the brain, suggests three main anatomical sites of action of drugs in mental disease:

1) Nigrostriatal pathway: motor function (M)

2+3) Mesocortical and mesolimbic pathway:

affect or emotional content, behavior (A+B)

4) Hypothalamus (tuberoinfundibular pathway):

control of autonomic nervous system and endocrine (prolactin release) (E)

M

A+B

E

III. Adverse effects1. Special Neurologic Effects 1) Extrapyramidal motor disorder

--bradykinesia (運動遲緩 ), tremor, muscle rigidity and akathisia (靜坐不能 ) (as like as parkinsonian syndrome)

2) Tardive dyskinesia (遲發性運動困難 )--involuntary and excessive oral-facial movements

3) Neuroleptic malignant syndrome --fever, muscle rigidity and cardiovascular system instability

--fatal!! (Tx: bromocriptine or dantrolene)

Bromocriptine PD: a direct dopamine agonist (at high dosage)

Tx: 1) Parkinson’s disease 2) Antipsychotic-induced

hyperprolactinemia and

neuroleptic malignant syndrome

3) Cocaine withdrawal and depression

PK: GI—Liver—the bile (5 mg tid/45 mg max)

Drug interaction: Ergot alkaloids

(hypertension and myocardial infarction)

2. A wide range of non-neuronal adverse effects of typical antipsychotic drugs:1) Drowsiness

(histamine receptor blockade)2) Dry mouth and blurred vision

(muscaranic receptor blockade)3) Orthostatic hypotensioon

(α1-adrenergic receptor blockade)

Choice of Antipsychotics

Life is like an onion, Life is like an onion, which one peels crying.which one peels crying.

French proverb

Jackson Pollock (1912-1956)

Drugs for the Treatment of Affective (Mood) Disorders

Therapeutic overview1) Affective disorders include major depression

and mania (or bipolar manic-depressive illness), are characterized by changes in mood as the primary clinical manifestation.

2) Major depression is characterized by feelings of intense sadness and despair, self-deprecation (自我否定 ). As many as 10% to 15% of indivuals with this disorder display suicidal behavior during their lifetime