Classifications of Antipsychotics.

Typical Antipsychotics or first-generation (conventional)

Also called typical, conventional or traditional antipsychotic agents
Their antipsychotic effects reflect competitive blocking of D2 receptors
More likely to be associated with extra pyramidal side effects (EPS) or movement disorders, such as Parkinsonism, neck stiffness, protrusion of the tongue, upward eyeball rolling.
This is most common with the highly potent drugs.
Primarily improve positive symptoms of schizophrenia
Low potency typical antipsychotics have less affinity for the D2 receptors but tend to interact with non dopaminergic receptors resulting in more cardio toxic and anti-cholinergic adverse effects including sedation, hypotension.

These are the most commonly used drugs in Uganda because they are cheap and available. Typical antipsychotics are more effective in the treatment of positive symptoms than the negative symptoms.

Mechanism of Action

Predominantly block dopamine D2 receptors in the mesolimbic system of the brain. Also blocks:

Muscarinic acetylcholine receptors
Histamine H1 receptors
Αlpha adrenoreceptors

The binding affinity of the typical is very strongly correlated with clinical antipsychotic and extrapyramidal potency: the typical antipsychotic drugs must be given in sufficient doses to achieve 60% occupancy of striatal D2 receptors

Classes of Typical Antipsychotics

Phenothiazines.
Butyrophenones.
Thioxanthones.

Phenothiazines

Chlorpromazine (Thorazine)(Largactil)
Fluphenazine (Prolixin)
Perphenazine (Trilafon)
Prochlorperazine (Compazine)
Thioridazine (Mellaril)
Trifluoperazine (Stelazine)
Mesoridazine
Promazine
Triflupromazine (Vesprin)
Levomepromazine (Nozinan)
Promethazine (Phenergan)

Chlorpromazine (Largactil)

Chlorpromazine it is in a phenothiazine group. It has high sedating properties but with low extra pyramidal side effects. It is absorbed in the jejunum (in alimentary canal) and metabolized in the liver. Anti- depressants reduces metabolism of chlorpromazine. Chlorpromazine works as a competitor for relevant enzymes.

Indications

Schizophrenia (psychotic disorders).
Mania.
Agitation in the elders.
Alcohol related problems (where there are no antipsychotic drugs i.e. haloperidol and thioridazine).
Intractable hiccups.
Nausea and vomiting
It can also control spasms in small doses i.e. in tetanus.

Contra-indications:

Liver diseases e.g. liver cirrhosis, bone marrow depletion, in glaucoma (increased pressure in the eye.)

N.B: Chlorpromazine can induce seizures it lowers the threshold of a seizure, so a fit chart should be put to observe that.

Dosage

Orally: Depending on the severity of psychosis, dosages can range from 100mg-1500mg in daily divided doses (DDD) as per prescription.

Injectables: This may range from 25-200mg IM. This may be given start depending on the severity of the condition. Or: It may be given continuous i.e. (continuous narcosis) i.e. 8 hourly or 12hourly, until the patient calms down, then oral treatment can be continued with.

Rectal suppository : Each suppository is of 100mg, this may be OD, BD, or TDS. It may be used in children above 5 years who cannot take drugs orally.

Syrups: This is 25mg/5mls. Suspension is also 100mg/5mls

Note: haloperidol and stelazine may be preferable in epileptic patients.

Piperazine e.g. Trifluoperazine (stelazine)

It is a neuroleptic of phenothiazine group. It has high extra pyramidal side effects and less sedating effects. It also has high properties of anti-hallucigenesis.

Indications:

Schizophrenia
Mania
Organic brain syndrome
Mental retardation with psychosis
Agitation in the elderly.
Severe anxiety.

Note: It’s a good drug in schizophrenic patients with negative features such as apathy, social with draw, lack of self drive.

Dosages

Oral tablets: 5-45mg in divided doses (DDD)

Injectable: 1-3mg IM. the maximum is usually 6mg, this may be given PRN.

Piperidine e.g. Thioridazine (melleril)

It is a neuroleptics in phenothiazine group. It has moderate sedating effects and less extra pyramidal side effects, but with high anti-cholinergic effects.

Indications:

Schizophrenia.
Mania.
Agitation in the elderly (moderate side effects)

N.B: Their regular blood pressure should be monitored.

Behavioral disorders associated with psychosis
Severe anxiety (it has also anxiolytic effect)

Contra-indications

As for chlorpromazine.

Dosage:

Give 100-1000mg in divided doses (DDD) depending on the severity of the condition.
Can also be given 1mg/kg body weight in children

Butyrophenones

Haloperidol (Haldol)
Pimozide (Orap)
Melperone
Benperidol
Triperidol

Haloperidol (haldol).

Generally, it has high extra pyramidal side effects but less sedating effects,

Indications

Mania (drug of choice)
Schizophrenia
Alcohol related problems.
Organic brain syndrome of any cause
Mental retardation with psychosis and agitation.
Nausea & vomiting
Hiccup

Contra indications:

As for chlorpromazine.

Dosage: 5-30mg is divided doses; the maximum dose can be 60mg DDD.

It is in tablets form: 0.1, 0.5, 1mg, 5mg, and 10mg

Injectables: 5mg-20mg IM start or continued narcosis i.e. 2hrly, 6hrly and 8hrly.

Dosage range for children: 25-50microgram.

Trifluperidol (triperidol)

Dose: 6-8mg OD/BD or TDS

Benperidol

It is very good in patients with deviant behavior (anti-social personality disorders)

Dose: 0.25-1.5mg OD, BD or TDS.

BLACKBOX WARNING

WARNING

See full prescribing information for complete Boxed Warning.

Increased Mortality in Elderly Patients with Dementia-Related Psychosis:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotics drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Haloperidol is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS).

Thioxanthones.

Chlorprothixene
Flupentixol (Depixol and Fluanxol)
Thiothixene (Navane)
Zuclopenthixol (Clopixol and Acuphase)

Thioxanthines are psychotropic drugs in the neuroleptics group. They were the first neuroleptics to come into use.

They are noted to have very gross side effects. With production of new neuroleptics drugs, the use of thioxanthines has reduced.

Indications:

Schizophrenia (chronic)
Mania
And other psychotic associated conditions.

Flupentixol (depixal)

Dose: 3mg-9mg. The maximum dose can be 18mg in divided doses

N.B: avoid giving neuroleptic injectables by I.V route for the fear of postural hypotension.

ANTIPSYCHOTIC DEPOT INJECTIONS (LONG ACTING)

These are antipsychotics given by injection I.M. They are oily in nature and therefore, slowly released and metabolized over a period of 2 weeks up to 4 weeks.

Indications

Chronic schizophrenia
Cases of persistent mania
Where there is total lack of oral medication compliancy in a psychotic patient.
When it can be consistently be maintained.

Give it concurrently with other oral treatment. However, it can be given alone as a maintained treatment.

Haloperidol decanoate (haldol decamate).

Dose: 50mg, 100mg-150mg (maximum) I.M. This is given monthly (4weeks).

Fluphenazine decanoate (modecate)

Initially with 12.5mg I.M stat if he is starting then 25mg-50mg for 2-4weeks

Fluspirilence (redeptin) 2mg/ml.

Give 2-4mg which is equivalent to 2mls. We can give 2mg in alternative days or weekly for one month (½) or 2months

Flupentixol decanoate (depixol)

It is very useful in patients with negative feature of schizophrenia. It has mood elevating effects.

Dose: Initially 20mg I.M, then after 10 days, increased to 40mg I.M 2-4 weekly.

Note:

Give a quarter or half stated doses in elderly.
After test dose, wait 4-10days before starting titration to maintenance therapy
Dose range is given in mg/week for convenience only avoid using shorter dose intervals than those recommended except in exceptional circumstances e.g. long interval necessitates high volume ( >3-4ml) injection.

Advice on prescribing depot injection/ medication: