PSYCHIATRIC MEDICATIONS

Dose Range of Oral Antipsychotics

Chlorpromazine	25- 1000
Trifluoperazine	10-50 mg
Thioridazine	150-800
Haloperidol	1.5-200
Droperidol	20-120 (qds)
Sulpiride	400-2400 (BD)
Respiridone	2-16 (BD)
Clozapine	25-900 (BD)
Olanzapine	10-20mg once
Quetiapine	400-750 (bd)

DEPOT I NJECTIONS

a) Indications

1. better patient compliance.

2. prophylaxis of bipolar disorder protects against hypomanic relapse.

(b) Side-effects

1. Initially a test dose injection to ensure no undue side-effects or idiosyncratic reactions

2. higher incidence of EPSE

Depot Dose Range

Depot Medication	Range	(Test) Weekly
Depixol	12.5 - 400	(20) mg
Modecate	6.25 - 50	(12.5)
Haldol	12.5 - 75	(12.5)
Clopixol	100 - 600	(100)

CLOPIXOL

Zuclopenthixol Decanoate

test 100mg

Range 100-600

Interval 2-4 Weeks

Useful in agitation and aggression

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DEPIXOL

Flupenthixol decanoate

test dose 20mg

range 12.5-400mg

interval 2-4 weeks

mood elevation

may worsen agitation

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HALDOL

Haloperidol Decanoate

Test 25 mg

12.5-75 mg every 4 weeks

High EPSE, Low sedation

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MODECATE

Fluphenazine Decanoate

Test 12.5

Range 6.25-50 mg every 2-5 weeks

High ESPE and aggravates depression

Equivalent Doses

DRUG	MG
Chlorpromazine	100
Thioridazine	=100
Fluphenazine	=2
Trifluoperazine	=5
Haloperidol	=3
Droperidol	=4
Sulpiride	=200
Clozapine	=50
Respiridone	=2
DEPOT	Weekly Inj.
Modecate	5
Piportil	10
Haldol	15
Depixol	10
Clopixol	100

ANTIPSYCHOTIC DRUG GROUPS

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1. Phenothiazines:

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(i) Aliphatic

(chlorpromazine).

(ii) Piperidine

(thioridazine) Melleril

(iii) Piperazine

(trifluoperazine) Stelazine

(fluphenazine) Modecate

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2. Butyrophenones

(haloperidol) Haldol

(droperidol).

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3. Thioxanthenes

(flupenthixol) Depixol

(zuclopenthixol). Clopixol/Acuphase

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4. Diphenylbutylpiperidine (pimozide).

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5. Substituted benzamides (sulpiride)

(amisulpride).

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6. Dibenzazepine (clozapine).

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7. Benzisoxazole (risperidone).

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8. Imidazolidinone (sertindole).

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9. Thienobenzodiazepine (olanzapine).

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10. Dibenzothiazepine (quetiapine).

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CHLORPROMAZINE

(a) Mode of action

1. Dopamine D2 antagonist in the mesolimbic cortical bundle

2. Other biochemical actions which mediate the side-effects :

(i) Dopamine blocking activity at other sites

(ii) Antiadrenergic

(iii) Anticholinergic

(iv) Antiserotonergic

(v) Antihistaminergic

(b) Indications

more sedative

less extrapyramidal S/Es, cf. haloperidol

N.B. In the elderly special dangers of hypotension, atropinic effects und ECG changes.

Terminal disease.

Anti-emetic.

Intractable hiccup.

I. Extrapyramidal (EPSEs) dopamine-blocking in the nigrostriatal pathway:

(i) Acute dystonia

(ii) Akathisia.

(iii) Pseudoparkinsonism.

(iv) Tardive dyskinesia.

2. Antiadrenergic:

(i) Postural hypotension.

(ii) Failure of ejaculation.

(iii) Sedation.

3. Anticholinergic:

(i) Dry mouth.

(ii) Blurred vision.

(iii) Constipation.

(iv) Urinary retention.

(v) Tachycardia.

(vi) Impotence.

(vii) Exacerbation of glaucoma.

4. Antiserotonergic : depression.

5. Antihistaminergic: sedation.

N.B. anti-adrenergic activity

6. Hyperprolactinaemia - dopamine blocking activity in the tubero-infundibular

7. Impaired temperature regulation:

(i) Hypothermia.

(ii) Hyperpyrexia.

8.Neuroleptic malignant syndrome (NMS).

9. Leucopenla.

10. Skin photosensitivity and pigmentation.

11. Cardiac arrhythmias.

12. Cholestatic jaundice.

13. Seizures

14. Weight gain.

HALOPERIDOL

Greater dopamine blocking activity& Less antiadrenergic activity than chlorpromazine with less anticholinergic activity.

(b) Indications

Drug of choice for:

1. Mania.

2. Acute organic disorder during the daytime.

3. Bringing acutely disturbed behaviour under immediate control - since it is less sedative and causes less postural hypotension than chlorpromazine.

4. Other non-affective psychoses.

cf. Chlorpromazine

1. More EPSE.

2. Less sedation

3. Less postural hypotension.

4. Less anticholinergic side-effects.

5. NMS - a particular problem with haloperidol if a daily dosage in excess of 2Omg q.d.s. is combined with lithium carbonate at a serum level of greater than 1.0 mmol/l.

6. Danger of severe EPSE with haloperidol if a daily dose in excess of 20 mg is combined with lithium carbonate at a serum level of greater than 0.8 mmol/I.

7. ECG changes at high dose

DROPERIDOL

(a) Mode of action

Similar to haloperidol (but with more antiadrenergic activity).

(b) Indications

1. Useful in manic patients who fail to respond to halo-peridol.

2. Useful in agitated manic patients who require rapid calming.

Similar to haloperidol (but with more postural hypotension).

TRIFLUOPERAZINE

(a) Mode of action

1. Greater dopamine blocking activity.

2. Less antiadrenergic activity. cf. chlorpromazine

3. Less anticholinergic activity. I

(b) Indications

1. Useful in psychotic patients where sedation is undesirable (i.e. retarded psychotic patients) - since it is less sedative - cf. chlorpromazine.

2. Useful in psychotic patients with intractable auditory hallucinations; usual dose range 5 mg b.d. to 5 mg t.d.s.

1. More EPSE.

2. Less sedation.

3. Less postural hypotension. J

4. Less anticholinergic side-effects.

SULPIRIDE

1. Low doses - block presynaptic dopamine autoreceptors (D3 and D4 receptors).

2. High doses - blocks postsynaptic dopamine receptors

more specific blocker of D2 receptors

(b) Indications

1. Low doses - negative symptoms such as apathy and social withdrawal (optimum dosage 4OOmg b.d.).

2. High doses -florid positive symptoms such as delusions and hallucinations (optimum dosage 8OOmg b.d.).

1. Less EPSE

2. Less sedation

3. Galactorrhoea.

THIORIDAZINE

(a) Mode of action

1. Less dopamine blocking activity. cf. chiorpro

2. Greater antiadrenergic activity.

3. Greater anticholinergic activity. mazine

(b) Indications

Particularly useful in elderly patients for psychotic symptoms and agitation (since less EPSE - cf. chlorpromazine).

1. Less EPSE.

2. More sedation.

3. More postural hypotension.

4. More anticholinergic side-effects.

5. Retinitis pigmentosa - particularly induced by thioridazine (at daily doses above 800 mg).

6. ECG changes (prolongation of the QT interval) associated with a possible increased risk of cardiotoxicity. In view of this, CSM recommends an ECG prior to commencing treatment in elderly patients.

7. Special danger in elderly patients of increasing confusion (an atropinic effect).

CLOZAPINE

Day	MANE	NOCTE	DOSEAGE
1		12.5
2	12.5	12,5
3	25	25	For 2 days
6	25	50	For 2 days
8	50	50	For 2 days
10	75	75	For 2 days
11	100	100	For 2 days
13	125	125	For 2 days
15	150	150	For 3 days
18	150	200	For 3 days
21	200	200	For 3 days

(a) Mode of action

1. Weak affinity for D2

2. More active at D4

3. Greater antia@renergic

4. Greater anticholinergic

5. High affinity for serotonergic receptors.

(b) Indications

schizophrenia in patients unresponsive to, or intolerant of, at least one drug from two chemically distinct conventional antipsychotic drugs given a full therapeutic trial; in addition, it may be worth considering a course of electroconvulsive therapy (ECT) before starting clozapine therapy.

1 Less EPSE.

2. More sedation.

3. More postural hypotenslon.

4. More anticholinergic side-effects.

5- agranulocytosis (life-threatening) in 2-3% of patients - restricted to patients registered with the clozaril patient monitoring service (CPMS)

patient has regular full blood counts

6. Hypersalivation.

7. Rare instances of myocarditis.

OLANZAPINE

I. Moderate affinity for D2 dopamine receptors; it preferentially blocks D2 receptors in the mesolimbic cortical

bundle

2. High affinity for 5-HT2 serotonin receptors.

3. Low affinity for a1-adrenergic receptors.

4. High affinity for muscarinic receptors.

(usual dose10mg daily; dose range 5-20 mg for maintenance treatment).

(once-per-day dosing).

1. Less EPSE (at doses of 5-10mg daily) this benefit may be lost at doses over 10mg daily.

2. Some ECG changes (prolongation of the QT interval)

3. Some postural hypotension. However, treatment can be initiated at a therapeutic dose (l0mg daily) without the need to build up from a starting dose, cf. risperidone, sertindole and quetiapine.

4. No agranulocytosis

5. Some disturbance in LFTs

6. Sometimes elevation in prolactin level. However, associated clinical manifestations are rare

7. weight gain and somnolence.

AMISULPRIDE

1. Blocks D3 (presynaptic) and D2 (postsynaptic).

2. Limbic selective.

3. Low affinity for 5-HT

4. Low affinity for a1-adrenergic

5. Low affinity for muscarinic

(b) Indications

I. Negative symptoms

(optimum dosage l00mg once a day).

2. Positive symptoms or a mixture of positive and negative symptoms (usual dose range 200mg b.d. to 400mg b.d.; maximum dosage 600mg b.d.).

1.Lower potential for EPSE, (not @ maximum dosage).

2. Some ECG changes

3. Some postural hypotension. However, treatment can be initiated at a therapeutic dose

(200mg b.d. for positive symptoms with or without negative symptoms)

no need to build up dose,

cf. risperidone, sertindole and quetiapine.

4. No agranulocytosis,

5. No LFTs.

6. Reversible hi prolactin

insomnia, anxiety and agitation.

RISPERIDONE

(a) Mode of action

I. Potent D2 antagonist preference for blocking D2 receptors in the mesolimbic cortical bundle

2. Potent 5-HT2 antagonist.

3. Potent a1-adrenergic receptor antagonist.

4. Potent H1-histamine antgonist.

(b) Indications

1 positive and negative symptoms of schizophrenia (usual dose range 2 mg b.d.4mg b.d.).

1. Less EPSE (at doses up to and including 5mg b.d.), this benefit is lost at doses

over 5 mg b.d.

2. More akathisia

3. Postural hypotension - when initiating treatment, the starting dose is 1 mg b.d. which is then increased over 3 days to 3 mg b.d.

4. nausea, dyspepsia, abdominal

pain.

5. No agranulocytosis

6. Significant elevation in prolactin level

7. sedation.

PIMOZIDE

More specific blocker of D1 and D2 receptors

1. Useful in maintenance treatment of schizophrenia Long half-life, it need only be taken once a day to prevent relapse of schizophrenia (dose range 2-20 mg daily).

2. Useful in monosymptomatic delusional psychosis/monosymptomatic hypochondriacal delusions (dose range 4-l6mg daily).

N.B. Special caution is needed over rate of rise in daily doses.

1. Less EPSE

2. Less sedation

3. Reports of sudden unexplained death, CSM recommends:

(i) An ECG prior to commencing treatment in all patients.

(ii) ECGs at regular intervals in patients taking over l6mg daily.

A review of the need for pimozide if arrhythmias develop.

PROLACTIN

Released by ant. pituitary to enlarge and prepare breast for lactation, it suppresses gonadotrphin secretion leading to amenorrhea; anovulatory cycles; and impotence in men.

Normal level is 15ng/ml, 200ng during pregnancy.

Dopamine suppress release of prolactin. All standard neuroletics block dopamine receptors in hypothalamus and raise prolactin levels as high as 5-10 times. The atypical neuroleptics have lesser effect. Prolactin level is dose dependent with Respiridone, transient with Olanzapine and non-existant with Clozapine and Quetiapine.

Levels remain high 2 weeks after stopping oral and six months after depot neuroleptics.

Sexual dysfunction includes anorgasmia, impotence and irregular menses. These occur in 50% of men and1/3 of women. Decreased libido occurs in 37 % of both.

Sexual side-effects are rated the worst and lead to non-compliance.

QUETIAPINE

SEREQUEL

DOSAGE.

Day 1 25mg bd

Day 2 50mg bd

Day 3 100mg bd

Day 4 150mg bd

Day 5 200mg bd

continue for 6 weeks

if no improvement incr. Upto 750mg daily

(375mg bd)

1. Weak affinity for D2 -

similar to clozapine.

2. High affinity for 5-HT2

3. High affinity for a1-adrenergic receptors.

4. No appreciable affinity for muscarinic receptors.

(b) Indications

I. Treatment of the symptoms of schizophrenia (positive, negative and affective).

(twice-per-day dosing; usual dose range

150mg b.d. to 225mg b.d. for maintenance treatment).

1. EPSE comparable with placebo across the dose range (up to, and including, the maximum dose of 375 mg b.d.).

2. Some ECG changes (prolongation of the QT interval).

3. Postural hypotension - therefore when initiating treatment, the starting dose is 25 mg b.d., which is then

increased over four days to 150mg b.d. in adults.

4. Not associated with agranulocytosis cf. clozapine.

5. Some disturbance in LFTs. However, there is no requirement for the routine monitoring of LFTs.

6. Prolactin level comparable with placebo across the dose range (up to, and including, the maximum dose).

7. Side-effects include headaches and somnolence.

(Zuclopenthixol acetate) ACUPHASE

Short-acting injection administered intramuscularly as an oily injection and rapidly released into the bloodstream.

Useful for immediate management of acutely disturbed behaviour as an alternative to haloperidol since:

I. more sedative than haloperidol.

2. A short course of these injections (maximum of four) is more easily administered

Treatment duration should not exceed 2 weeks with a maximum dosage of 150mg for each injection and a maximum dosage of 400 mg for each course of injections.

Zuclopenthixol dec. CLOPIXOL

(a) Indications

I. Useful in agitated or aggressive schizophrenic patients.

2. May be useful for the control of aggressive patients

(more sedative than fluphenazine decanoate).

(b) Adverse effects

exacerbate psychomotor retardation

Flupenthixol decanoate DEPIXOL

1. Useful in treating retarded or withdrawn schizophrenic patients

2. antipsychotic depot injection of choice in patients with bipolar affective disorder - mood-elevating effect

(b) Adverse effects

Not suitable for agitated or aggressive schizophrenic patients - it can cause over-excitement

Fluphenazine decanoate MODECATE

1. Useful in treating agitated or aggressive schizophrenic patients.

2. useful for the control of aggressive patients (in view of its sedative nature).

(b) Adverse effect

Contraindicated in severely depressed states - in view of its tendency to cause depression.

MOOD STABILISERS

LITHIUM CARBONATE

(i) Enhances the effects of antidepressants

(ii) with SSRIs - risk of the serotonin syndrome developing (enhanced serotonergic activity); this risk appears to be lowest with fluvoxamine.

(i) In unipolar disorders:Lithium reduces the rate of relapse (not more effective than continuing antidepressants).

(Continuing treatment with lithium reduces the rate of relapse after treatment with ECT.

(ii) In bipolar affective disorders - prolonged administration of lithium (5 years) prevents relapses into depression.

3. Treatment of mania:

Lithium is effective in high doses (l000mg nocte), but the therapeutic response usually only occurs in the second week of treatment; Plus, the response to lithium is slower than the response to antipsychotic drugs.

4. Preventing relapse of mania:

In bipolar affective disorders. prolonged administration of lithium (5 years) prevents relapses into mania.

5 Mixed affective states.

6. Schizoaffective disorders - with an antipsychotic depot injection.

7. Aggressive or self-mutilating behaviour.

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I.Short-term side-effects:

(i) Gastrointestinal disturbances (nausea, vomiting, diarrhoea).

(ii) Fine tremor.

(iii) Muscle weakness.

(iv) Polyuria.

(v) Polydypsia.

2. Long-term side-effects:

(i) Nephrogenic diabetes insipidus.

(ii) Hypothyroidism.