Second edition

20.qxd 3/10/08 9:58 AM Page 613
and dramatic and stormy emotions; when under great stress,
these patients may at times also develop delusions, either of
persecution or reference, and may also experience auditory
hallucinations. The distinction from schizophrenia rests on
the stormy instability that characterizes these patients’ lives
and on the fact that the psychotic symptoms appear only at
times of great stress; this is in contrast to schizophrenia, in
which they are present throughout the course, even during
stress-free periods. Schizotypal personality disorder is characterized
by chronic aloofness and by peculiar thoughts and
behavior, and thus may mimic simple schizophrenia. The
differential here rests on the overall course: in the personality
disorder there is no deterioration, whereas in simple schizophrenia
one sees a very slow progression.
Schizophreniform disorder and brief psychotic disorder
(also known as brief reactive psychosis) are both characterized
by symptoms that are similar to those seen in schizophrenia;
however, where they differ is in their supposed
course. Patients who experience a full, complete, and spontaneous
remission within 1 month are said to have brief
psychotic disorder, whereas those whose illness lasts longer
than 1 month but less than 6 months are said to have
schizophreniform disorder. However, there is a debate as
to whether such disorders actually exist. Certainly, there
are patients with schizophrenia who are treated with
antipsychotics early in the course of the illness and who
experience a complete, antipsychotic-induced remission of
symptoms; however, in these cases, if treatment is discontinued,
symptoms gradually recur. What is at issue here is
whether there are, in fact, cases in which symptoms spontaneously
and completely undergo a lasting remission
without treatment. I have never seen such a case, nor am I
aware of any such well-documented cases in the literature.
Other causes of psychosis are discussed in Section 7.1
and, although most of these are rare, the reader is encouraged
to gain familiarity with them.
Treatment
In almost all cases, treatment involves the use of an
antipsychotic drug. These agents may be broadly divided
into two different categories, namely first-generation and
second-generation or, as they are often also termed, typical
and atypical agents.
First-generation agents are further subdivided into
‘high-potency’ (haloperidol, fluphenazine, perphenazine,
trifluoperazine, and thiothixene), ‘low-potency’ (chlorpromazine
and thioridazine), and ‘medium-potency’
(loxapine and molindone) drugs. High-potency drugs
require lower milligram doses and are more likely to cause
extrapyramidal side-effects (e.g., parkinsonism, dystonia,
akathisia, akinesia). Low-potency drugs require higher
doses and are less likely to cause extrapyramidal sideeffects,
but are prone to cause sedation, hypotension, and
anticholinergic effects. Medium-potency drugs, as might
be expected, fall in-between regarding both milligram
20.1 Schizophrenia 613
dosage and side-effects. Of these first-generation agents,
both haloperidol and fluphenazine are available in intramuscular
‘depot’ formulations, which are given, on average,
once every 4 or 2 weeks respectively. All other things
being equal, of the first-generation agents, haloperidol is
probably a reasonable first choice.
Second-generation agents include clozapine, olanzapine,
risperidone, quetiapine, aripiprazole, and ziprasidone.
Choosing among these agents is not straightforward. With
regard to effectiveness, clozapine is clearly superior; however,
its side-effect profile, especially the risk of agranulocytosis,
limits its use to treatment-resistant cases. Of the other
agents, although there is controversy here, it appears that
olanzapine may have an edge in terms of overall effectiveness
(Lieberman et al. 2005). This advantage, however, is severely
tempered by the tendency of olanzapine to cause metabolic
derangements, including weight gain, hyperlipidemia, and
diabetes. Both risperidone and quetiapine may also cause
these metabolic derangements, but are much less likely to do
so; risperidone, alone among the second-generation agents,
is available in a long-acting intramuscular ‘depot’ formulation,
providing benefit for 2 weeks. Aripiprazole and ziprasidone
stand out in that they are not associated with metabolic
changes. Overall, and all other things being equal, if a secondgeneration
agent is used, it may be reasonable to start with
risperidone; however, again, it must be acknowledged that
this is an area of great controversy.
In deciding which antipsychotic, whether first or second
generation, to prescribe, the first step is to obtain an accurate
treatment history, and this may require not only questioning
the patient but also reviewing records and interviewing family
members. If there is a history of a good response combined
with good tolerability, then it makes sense to use the
same drug again. In treatment-naive patients, or in cases in
which prior treatments were unsatisfactory, other considerations
come into play. Although not without controversy, it
appears that, overall, second-generation agents are more
effective and better tolerated than first-generation ones, and,
consequently, it may be reasonable to select a second-generation
agent. Of the second-generation agents, risperidone, as
noted above, is a reasonable choice, both regarding efficacy
and side-effects, and this also allows one to move to intramuscular
‘depot’ treatments in cases of non-compliance. It
must be emphasized, however, that the choice of an agent is
not simple or straightforward, and often multiple trials of
different agents must be performed before a regimen is
found that is reasonably effective and well-tolerated.
Regardless of which agent is chosen, it is important that
one gives it an ‘adequate’ trial before moving on to another,
not only in terms of dose but also duration. In general,
assuming an adequate dose is used, one should observe the
patient for at least 2 weeks to get a reasonable idea as to
response. In cases characterized by significant agitation, one
may, as described in Section 6.4, consider adding adjunctive
lorazepam to either risperidone or haloperidol, and continuing
this until the agitation has passed, after which the
patient may be continued on the antipsychotic alone. If the