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Clinician’s Corner: 1st Generation Antipsychotic Drugs

This class of drugs as discussed last week is responsible for the emptying out of the state mental hospitals.  My wife Denise volunteered at the Hollidaysburg State Mental Hospital and described the patients all had the same appearance.  All of them smoked, had yellow tar stained fingers and hair from the constant cigarette smoke.  Smoking was encouraged in the schizophrenic population, as it helped manage symptoms.  Smoking however, also caused increased metabolism of the medications, and therefore higher doses were needed.

Nearly 90 percent of people with schizophrenia smoke, most of them being heavy smokers, and 60 to 70 percent of people with bipolar disorder also smoke. According to recent research in China, nicotine restores dynamic intrinsic brain activity of people with schizophrenia.  Maybe someday soon we’ll have the third generation of antipsychotics.

DOSAGE EQUIVALENTS AND SIDE EFFECTS OF TYPICAL ANTIPSYCHOTICS (FIRST GENERATION ANTIPSYCHOTICS)

DRUG NAME

YEAR

EQUIV DOSE USUAL ADULT DOSE SIDE EFFECT SIDE EFFECT SIDE EFFECT
      EPS AC SED
Chlorpromazine (Thorazine®)

1957

100mg 30-800mg ++ ++ +++
Fluphenazine (Prolixin )

1959

2mg 1-40mg ++++ + +
Mesoridazine (Serentil®)

1970

50mg 100mg-400mg + +++ +++
Perphenazine (Trilafon®)

1957

10mg 12-64mg ++ + +++
Thioridazine (Mellaril®)

1962

100mg 150-800mg + +++ +++
Trifluoperazine (Stelazine®)

1959

5mg 2-15mg +++ + +
Thiothixine (Navane®)

1967

4mg 6-60mg +++ + +
Molindone (Moban®)

1974

10mg 20-150mg ++ + +
Loxapine (Loxitane®)

1975

10mg 20-250mg ++ + +
Haloperidol (Haldol®)

1967

2mg 1-100mg ++++ + +

SIDE EFFECT ABBREVIATIONS:

EPS: extrapyramidal side effects

AC: anticholinergic side effects—note the more anticholinergic side effects, the less EPS

SED: sedation or drowsiness.

Prescribing notes:

  • These first-generation agents work in the central nervous system by blocking dopamine-2 (D2) receptors, which have the potential to cause Parkinson like side effects.
  • In general, efficacy in treating patients with schizophrenia is similar for all of these agents. They differ by side effect profiles.
  • First generation antipsychotics are implicated with weight gain, possibly due to:
    • Increased appetite due to serotonin receptors and dopamine receptor blockade
    • Increased drowsiness and decreased physical activity due to histamine blockade
    • Weight gain:  weight gain does not appear to be dose related
    • The main differences between first and second-generation antipsychotics is that first-generation antipsychotics have significant potential to cause extrapyramidal side effects and tardive dyskinesia

Tardive dyskinesia: 

abnormal involuntary stereotyped movements of the face, mouth, trunk and limbs. May occur months or years (usually) after treatment.  Affects 20-35% of treated patients. See a cumulative rate of 5% per year.

Predisposing factors:    older age, years of treatment, cigarette smoking & diabetes

Emphasis is on prevention.

Prolactin Elevation:

All typical antipsychotics elevate prolactin levels. Remember dopamine puts the brakes on prolactin, therefore blocking dopamine allows prolactin to be released in higher amounts. Prolactin levels two to three times higher than normal are seen. Elevated prolactin levels cause menstrual irregularities, infertility, loss of sexual desire, and erectile and ejaculatory dysfunction.

Extrapyramidal symptoms:

Characterized by the desire to be in constant motion, followed by the inability to sit or stand still, and consequent pacing.  Increase incidence in women who smoke.