Augmentation of Typical Neuroleptics
When a
patient has shown an inadequate response to traditional neuroleptic agents from
different classes and there is a good rea-son for not switching to a novel
antipsychotic drug, other strate-gies may be necessary to ameliorate residual
symptoms. Adding a different type of psychotropic medication may augment the
neu-roleptic response in some individuals. Several neuroleptic aug-mentation
strategies have been studied, including the addition of beta-blockers,
thyrotropin-releasing hormone, clonidine and val-proic acid, with mixed
results. Lithium has been evaluated exten-sively for its efficacy as an
additional treatment of schizophrenia. In one study, lithium seemed to improve
psychotic symptoms of patients who had not adequately responded to neuroleptics
alone (Small et al., 1975). Although lithium does not seem to affect
positive or negative symptoms specifically, it may be beneficial for patients
who present at the depressed end of the spectrum (Meltzer, 1992). Similarly,
carbamazepine has had mixed results as an augmentation agent although there is
evidence that it can improve anxiety, withdrawal and depression. The use of
benzodi-azepines as augmenting agents in the treatment of schizophrenia has
also been extensively studied. There may be some patients who show improvement
in psychotic symptoms, and others who show improvement in negative symptoms.
Interestingly, there has been a suggestion that the triazolobenzodiazepines may
be more effective than other types of benzodiazepines in augment-ing the
neuroleptic response.
Antidepressant medications have also been considered in the treatment of
depression associated with schizophrenia. Al-though there is some evidence that
typical neuroleptics them-selves cause depression there undoubtedly are
schizophrenic patients who have primary depressive symptoms. Negative symp-toms
are often difficult to distinguish from depression (both have features of
amotivation, apathy and social withdrawal), but those that are secondary to
depression may respond to the addition of an antidepressant to the patient’s
medication regimen.
With electroconvulsive therapy as an adjuvant treatment, it appears the
patient may improve initially, but relapse is likely. However, patients with
comorbid affective symptoms may have some increased benefit. In general,
however, this option should be considered only if the patient is not a
candidate for a trial with an atypical antipsychotic agent and only if the
patient has severe persistent symptoms.
When
agonists of the glycine site of the NMDA receptor were added to typical
antipsychotic agents in a placebo-controlled study, significant improvement
were reported in negative symp-toms and aspects of cognitive functioning
(Heresco-Levy et al., 1999). D-cycloserine,
a partial agonist at the glycine site pro-duced a selective improvement of
negative symptoms at 6 weeks (Goff et al., 1999). Augmentation with another endogenous full
agonist, D-serine was associated with
significant improvement in negative, positive, and cognitive symptoms when
added to con-ventional agents in an 8-week trial (Tsai et al., 1998).
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