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either orally or intramuscularly. The use of benzodiazepines may also reduce the amount
of antipsychotic that is needed to control psychotic patients.
Some studies suggest that a longer time between the first onset of psychosis and
the initiation of treatment is related to a worse outcome. As a result, clinicians must
consider the possibility that delayed treatment may worsen the patient's prognosis.
However, these data do not mean that all patients need to be treated immediately. A brief
delay may permit clinicians to develop a more thorough diagnostic evaluation and rule
out causes of abnormal behavior, such as substance abuse, extreme stress, medical
illnesses, and other psychiatric illnesses.
indefinite basis.
Noncompliance
Noncompliance with long-term antipsychotic treatment is very high. An estimated
40 to 50 percent of patients become noncompliant within 1 or 2 years. Compliance
increases when long-acting medication is used instead of oral medication.
When beginning long-acting drugs, some oral supplementation is necessary while peak
plasma levels are being achieved. Fluphenazine and haloperidol have been formulated as
long-acting injectables. A long-acting form of risperidone is also available.
There are a number of advantages to using long-acting injectable medication. Clinicians
know immediately when noncompliance occurs and have some time to initiate
appropriate interventions before the medication effect dissipates; there is less day-to-day
variability in blood levels, making it easier to establish a minimum effective dose; and
finally, many patients prefer it to having to remember dosage schedules of daily oral
preparations.
Dosing
The clinically effective dose for treatment depends on the characteristics of the
drug and patient factors, such as inherited sensitivity and ability to metabolize a drug,
concurrent medical disorders, use of concurrent medications, and history of exposure to
previous medications.
Plasma concentrations of many psychotropics can vary up to tenfold. Thus, to
some extent, the optimal dose for an individual is ultimately determined by trial and
error, guided by the empirical evidence of the usual dose range for that drug. Some drugs
demonstrate a clear relationship between increases in dose and clinical response. This
dose- response curve plots the drug concentration against the effects of the drug.
The potency of a drug refers to the relative dose required to achieve certain
effects, not to its efficacy. Haloperidol, for example, is more potent than chlorpromazine,
Duration of Treatment
A common question from a patient: How long do I need to take the medication?
The answer depends on multiple variables, including the nature of the disorder, the
duration of symptoms, the family history, and the extent to which the patient tolerates and
benefits from the medication. Patients can be given a reasonable explanation of the
probabilities but should be told that it is first best to see if the medication works for him
or her and whether the side effects are acceptable. Any more definitive discussion of
treatment duration can be held once the degree of success is clear. Even patients with a
philosophical aversion to the use of psychotropic drugs may elect to stay on medication
indefinitely if the magnitude of improvement is great. Most psychiatric disorders have
high rates of chronicity and relapse. Because of this, long-term treatment is often needed
to prevent recurrence. Nevertheless, the fact remains that psychotropic drugs are not said
to cure the disorders they treat, but rather to help control the symptoms.
Treatment is conceptually broken down into three phases: the initial therapeutic
trial, the continuation, and the maintenance phase. The initial period of treatment should
last at least several weeks because of the delay in therapeutic effects that characterizes
most classes of psychotropic drugs. The required duration of a therapeutic trial of a drug
should be discussed at the outset of treatment, so that the patient does not have unrealistic
expectations of an immediate improvement in symptoms. Patients are more likely to
experience side effects early in the course of pharmacotherapy than any relief from their
disorder. In some cases, medication may even exacerbate some symptoms. Patients
should be counseled that a poor initial reaction to medication is not an indicator of the
ultimate outcome of treatment. For instance, many patients with panic disorder develop
jitteriness or an increase in panic attacks after starting on tricyclic or SSRI treatment.
Benzodiazepine agonists are an exception to the rule that clinical onset is delayed. In
most cases, their hypnotic and antianxiety effects are evident immediately.
Ongoing use of medication, however, does not provide absolute protection against
relapse. Continuation therapy provides clinically and statistically significant protective
effects against relapse. The optimal duration of continuation or maintenance therapy is
variable and dependent on the clinical history of the patient. Early-onset chronic major
depression, for example, has a more severe course and greater comorbidity than lateonset chronic major depression. In addition to early onset, a history of multiple past
episodes, and severity and length of current episode would make longer, even indefinite,
treatment appropriate.
Risperidone
Pharmacology
Risperidone is a benzisoxazole. Risperidone undergoes extensive first- pass
hepatic metabolism to 9-hydroxyrisperidone, a metabolite with equivalent antipsychotic
activity. Peak plasma levels of the parent compound occur within 1 hour for the parent
compound and 3 hours for the metabolite. Risperidone has a bioactivity of 70 percent.
The combined half-life of risperidone and 9-hydroxyrisperidone averages 20 hours, so it
is effective in once-daily dosing. Risperidone is an antagonist of the serotonin 5-HT
2A
Side Effects
Extrapyramidal effects of risperidone are largely dosage dependent, and a trend is
seen to using lower doses than initially recommended. Weight gain, anxiety, nausea and
vomiting, rhinitis, erectile dysfunction, orgasmic dysfunction, and increased pigmentation
are associated with risperidone use. The most common drug-related reasons for
discontinuation
of
risperidone
use
are
extrapyramidal
symptoms,
dizziness,
hyperkinesias, somnolence, and nausea. Marked elevation of prolactin can occur. Weight
gain occurs more commonly with risperidone use in children than in adults.
Dosages
The recommended dose range and frequency of risperidone dosing has changed
since the drug first came into clinical use. Risperidone is available in 1-, 2-, 3-, and 4-mg
tablets, and a 1-mg/mL oral solution and in M-tab form (rapidly dissolving). The initial
dosage is usually 1 to 2 mg at night, which can then be raised to 4 mg per day. Positron
emission tomography (PET) studies have shown that dosages of 1 to 4 mg per day
provide the required D blockade needed for a therapeutic effect. At first it was believed
2
that because of its short elimination half- life, risperidone should be given twice a day,
but studies have shown equal efficacy with once-a-day dosing. Dosages above 6 mg a day
are associated with a higher incidence of adverse effects, particularly extrapyramidal
symptoms. No correlation has been found between plasma concentrations and therapeutic
effect.
Risperidone (Risperdal Consta) is the only SDA currently available in a depot
formulation. It is given as an intramuscular (IM) injection formulation every 2 weeks.
The dose may be 25, 50, or 75 mg. Oral risperidone should be coadministered with
Risperdal Consta for the first 3 weeks before being discontinued.