ANTIPSYCHOTIC DRUGS &
The term antipsychotic is applied to a group of
drugs commonly but not exclusively used to treat psychosis. Common
conditions with which antipsychotics might be used include schizophrenia,
bipolar disorder, mania, autism spectrum disorders and delusional
research on anti-psychotics
Although no medication acts a 'cure' for Autism
Spectrum Disorders, typical and atypical anti-psychotics have proved
to be the most effective medication for reducing the overall symptoms
to date. Their use in not wide spread due to side-effects, particularly
with long-term use.
Typical anti-psychotics such as haloperidol, fluphenazine,
and thioridazine, were actually developed to treat schizophrenia.
They help to manage symptoms of Autism Spectrum Disorders but possible
side effects include stiffness, restlessness and involuntary movements.
Long-term use can result in permanent tardive dyskinesia (Sikich
Research has focused on atypical antipsychotics,
especially risperidone, which has the largest amount of evidence
that consistently shows improvements in irritability, self-injury,
aggression, and tantrums associated with ASD. In the United States,
risperidone is approved for treating symptomatic irritability in
autistic children and adolescents aged 5–16 years. In short-term
trials (up to 6 months) most adverse events were mild to moderate,
with weight gain, drowsiness, and high blood sugar requiring monitoring.
Its long term efficacy and safety have not been fully determined.
It is unclear whether risperidone improves autism's core social
and communication deficits. As with most interventions for Autism
Spectrum Disorders, much more research is needed to accurately establish
these medications as evidence-based
Terminology of antipsychotics
Antipsychotics are also referred to as neuroleptic
drugs, neuroleptics. The word neuroleptic is derived from Greek,
the word means taking hold of one's nerves. This term reflects the
drugs' ability to make movement more difficult and sluggish, which
clinicians previously believed indicated that a dose was high enough.
The lower doses used currently have resulted in reduced incidence
of motor side-effects and sedation, and the term is less commonly
used than in the past.
Antipsychotics are broadly divided into two groups,
the typical or first-generation antipsychotics and the atypical
or second-generation antipsychotics. There are also dopamine partial
agonists, which are often categorized as atypicals.
Typical antipsychotics are also sometimes referred
to as major tranquilizers, because some of them can tranquilize
and sedate. This term is increasingly disused, as the terminology
implies a connection with benzodiazepines ("minor" tranquilizers)
when none exists.
Usage of antipsychotics
Common conditions with which antipsychotics might
be used include schizophrenia, mania and delusional disorder. They
might be used to counter psychosis associated with a wide range
of other diagnoses. Antipsychotics may also be used in mood disorder
(e.g. bipolar disorder) even when no signs of psychosis are present.
In addition, these drugs are used to treat non-psychotic disorders.
For example, some antipsychotics (haloperidol, pimozide) are used
off-label to treat Tourette syndrome; while abilify is prescribed
in some cases of Asperger's syndrome.
In routine clinical practice, antipsychotics may
be used as part of risk management, and to control difficult patients,
although this is controversial.
History of antipsychotics
The original antipsychotic drugs were happened
upon largely by chance and were tested empirically for their effectiveness.
The first antipsychotic was chlorpromazine, which
was developed as a surgical anesthetic. It was first used on psychiatric
patients in the belief that it would have a calming effect. However,
the drug soon appeared to reduce psychosis beyond this calming effect,
and now some believe that it causes a reduction of psychosis unrelated
to the sedating effect of the medication. It was introduced for
the treatment of psychosis during the period when lobotomy was a
common treatment and was hailed as a "cure" for schizophrenia.
It was then touted to provide a "chemical lobotomy," causing
similar neurological effects without requiring surgery.
The newer atypical antipsychotics are supposedly
rationally designed drugs in which a theoretical understanding of
both the condition to be treated and the effect of certain molecules
on the body is used to develop potential new drug candidates. However,
continued off-label use of the newer drugs indicates that old-fashioned
empirical drug discovery is still important in evaluating this class
* Clozapine (Clozaril) - Requires weekly to biweekly
CBC (FBC) because of risk of agranulocytosis (a severe decrease
of white blood cells).
* Olanzapine (Zyprexa) - Used to treat psychotic disorders including
schizophrenia, acute manic episodes, and maintenance of bipolar
disorder. Dosing 2.5 mg to 20 mg per day. Comes in a form that quickly
dissolves in the mouth (Zyprexa Zydis). May cause appetite increase,
weight gain and altered glucose metabolism leading to an increased
risk of diabetes mellitus.
* Risperidone (Risperdal) - Dosing 0.25 to 6 mg per day and is titrated
upward; divided dosing is recommended until initial titration is
completed at which time the drug can be administered once daily.
Available in long-acting form (Risperdal Consta that is administered
every 2 weeks; usual dose is 25 mg). Comes in a form that quickly
dissovles in the mouth (Risperdal M-Tab). Used off-label to treat
* Quetiapine (Seroquel) - Used primarily to treat bipolar disorder
and schizophrenia, and "off label" to treat chronic insomnia
and restless legs syndrome; it is a powerful sedative (if it's used
to treat sleep disorders and is not effective at 200 mg, it is not
going to be effective in this regard). Dosing starts at 25 mg and
continues up to 800 mg maximum per day, depending on the severity
of the symptom(s) being treated. Users typically take smaller doses
during the day for the neuroleptic properties and larger dose at
bedtime for the sedative effects, or divided in two equally high
doses every 12 hours (75-400mg bid).
* Ziprasidone (Geodon) - Now (2006) approved to treat bipolar disorder.
Dosing 20 mg twice daily initially up to 80 mg twice daily. Prolonged
QT interval a concern; watch closely with patients who have heart
disease; when used with other drugs that prolong QT interval potentially
* Amisulpride (Solian) - Selective dopamine antagonist. Higher doses
(greater than 400 mg) act upon post-synaptic dopamine receptors
resulting in a reduction in the positive symptoms of schizophrenia,
such as psychosis. Lower doses however act upon dopamine autoreceptors,
resulting in increased dopamine transmission, improving the negative
symptoms of schizophrenia. Lower doses of amisulpride have also
been shown to have anti-depressant and anxiolytic effects in non-schizophrenic
patients, leading to its use in dysthymia and social anxiety disorder.
In one particular study, amisulpride was found to have greater efficacy
than fluoxetine in decreasing anxiety. Currently, amisulpride is
approved in Europe, Australia and other countries for use in schizophrenia,
and is approved and marketed in lower dosages in some countries
for treating dysthymia (such as in Italy as Deniban). Amisulpride
has not been approved by the FDA for use in the United States.
* Paliperidone (Invega) - Derivative of risperidone. Approved in
* Dopamine partial agonists:
* Aripiprazole (Abilify) - Dosing 5 mg up to maximum of 30 mg has
been used. Mechanism of action is thought to reduce susceptibility
to metabolic symptoms seen in some other atypical antipsychotics.
* Under clinical development - Bifeprunox; norclozapine (ACP-104).
* Symbyax - A combination of olanzapine and fluoxetine
used in the treatment of bipolar depression.
* Tetrabenazine (Nitoman in Canada and Xenazine in New Zealand and
some parts of Europe) is similar in function to antipsychotic drugs,
though isn't generally considered an antipsychotic itself. This
is likely due to its main usefulness being the treatment of hyperkinetic
movement disorders such as Huntington's Disease and Tourette syndrome,
rather than for conditions such as schizophrenia. Also, rather than
having the potential to cause tardive dyskinesia that most antipsychotics
have, tetrabenazine can actually be an effective treatment for the
* Cannabidiol One of the main psychoactive components of cannabis.
A recent study has shown cannabidiol to be as effective as atypical
antipsychotics in treating schizophrenia. 
The most common typical antipsychotic drugs are
now off-patent, meaning any pharmaceutical company is legally allowed
to produce cheap generic versions of these medications. While this
makes them cheaper than the atypical drugs which are still manufactured
under patent constraints, atypical drugs are preferred as a first
line treatment because they are believed to have fewer side effects
and seem to have additional benefits for the 'negative symptoms'
of schizophrenia, a typical condition for which they might be prescribed.
Drug action of antipsychotics
All antipsychotic drugs tend to block D2 receptors
in the dopamine pathways of the brain. This means that dopamine
released in these pathways has less effect. Excess release of dopamine
in the mesolimbic pathway has been linked to psychotic experiences.
It is the blockade of dopamine receptors in this pathway which is
thought to control psychotic experiences.
Typical antipsychotics are not particularly selective
and also block Dopamine receptors in the mesocortical pathway, tuberoinfundibular
pathway and the nigrostriatal pathway. Blocking D2 receptors in
these other pathways is thought to produce some of the unwanted
side effects that the typical antipsychotics can produce (see below).
They were commonly classified on a spectrum of low potency to high
potency, where potency referred to the ability of the drug to bind
to dopamine receptors, and not to the effectiveness of the drug.
High potency antipsychotics such as haloperidol typically have doses
of a few milligrams and cause less sleepiness and calming effects
than low potency antipsychotics such as chlorpromazine and thioridazine,
which have dosages of several hundred milligrams. The latter have
a greater degree of anticholinergic and antihistaminergic activity
which can counteract dopamine-related side effects.
Atypical antipsychotic drugs have a similar blocking
effect on D2 receptors. Some also block or partially block serotonin
receptors (particularly 5HT2A, C and 5HT1A receptors):ranging from
risperidone which acts overwhelmingly on serotonin receptors, to
amisulpride which has no serotonergic activity. The additional effects
on serotonin receptors may be why some of them can benefit the 'negative
symptoms' of schizophrenia.
Side effects of antipsychotics
Antipsychotics are associated with a range of
side-effects. It is well recognized that many people (around two
thirds in controlled drug trials) discontinue antipsychotics, partly
due to adverse effects.
Extrapyramidal reactions include acute dystonias,
akathisia, parkinsonism (rigidity and tremor), tardive dyskinesia,
tachycardia, hypotension, impotence, lethargy, seizures, and hyperprolactinaemia.
The atypical antipsychotics (especially olanzapine)
seem to cause weight gain more commonly than the typical antipsychotics.
The well documented metabolic side effects associated with weight
gain include diabetes that, frequently, can be life threatening.
Clozapine also has a risk of inducing agranulocytosis,
a potentially dangerous reduction in the number of white blood cells
in the body. Because of this risk, patients prescribed clozapine
may need to have regular blood checks to catch the condition early
if it does occur, so the patient is in no danger.
One of the more serious of these side effects
is tardive dyskinesia, in which the sufferer may show repetitive,
involuntary, purposeless movements often of the lips, face, legs
or torso. It is believed that there is a greater risk of developing
tardive dyskinesia with the older, typical antipsychotic drugs,
although the newer antipsychotics are now also known to cause this
disorder. It is believed by some that the risk of tardive dyskinesia
can be reduced by combining the anti-psychotics with diphenhydramine
or benztropine, though this has not been established. Central nervous
system damage is also associated with irreversible tardive akathisia
and/or tardive dysphrenia.
Another antipsychotic side-effect is deterioration
of teeth due to a lack of saliva.
A potentially serious side effect of many antipsychotics
is that they tend to lower an individuals seizure threshold. Chlorpromazine
and clozapine particularly, have a relatively high seizurogenic
potential. Fluphenazine, haloperidol, pimozide and risperidone exhibit
a relatively low risk. Caution should be exercised in individuals
that have a history of seizurogenic conditions (such as epilepsy,
or brain damage).
Another serious side effect is neuroleptic malignant
syndrome, in which the drugs appear to cause the temperature regulation
centers to fail, resulting in a medical emergency as the patient's
temperature suddenly increases to dangerous levels.
Another problematic side effect of antipsychotics
Some people suffer few of the obvious side effects
from taking antipsychotic medication, while others may have serious
adverse effects. Some side effects, such as subtle cognitive problems,
may go unnoticed.
Efficacy of antipsychotics for mental disorders
There have been a large number of studies of the
efficacy of typical antipsychotics, and an increasing number on
the more recent atypical antipsychotics.
The American Psychiatric Association and the UK
National Institute for Health and Clinical Excellence recommend
antipsychotics for managing acute psychotic episodes and for preventing
relapse. They state that response to any given antipsychotic
can be variable so that trials may be necessary, and that lower
doses are to be preferred where possible.
Antipsychotic polypharmacy—prescribing two or
more antipsychotics at the same time for an individual—is said to
be a frequent practice but not necessarily evidence-based.
Some doubts have been raised about the long-term
effectiveness of antipsychotics because two large international
World Health Organization studies found individuals diagnosed with
schizophrenia tend to have better long-term outcomes in developing
countries (where there is lower availability and use of antipsychotics)
than in developed countries. The reasons for the differences
are not clear, however, and various explanations have been suggested.
Some argue that the evidence for antipsychotics
from withdrawal-relapse studies may be flawed, because they do not
take into account that antipsychotics may sensitize the brain and
provoke psychosis if discontinued. Evidence from comparison
studies indicates that at least some individuals recover from psychosis
without taking antipsychotics, and may do better than those who
do take antipsychotics. Some argue that, overall, the evidence
suggests that antipsychotics only help if they used selectively
and are gradually withdrawn as soon as possible.
A dose response effect has been found in one study
from 1971 between increasing neuroleptic dose and increasing number
of psychotic breaks.
Typical versus atypical antipsychotics
While the atypical, second-generation medications
were marketed as offering greater efficacy in reducing psychotic
symptoms while reducting side effects (and extra-pyramidal symptoms
in particular) than typical medications, these results showing these
effects often lack robustness. To remediate this problem, the NIMH
conducted a recent multi-site, double-blind, study (the CATIE project),
which was published in 2005. This study compared several atypical
antipsychotics to an older typical antipsychotic, perphenazine,
among 1493 persons with schizophrenia. Perphenazine was chosen because
of its lower potency and moderate side-effect profile. The study
found that only olanzapine outperformed perphenazine in the researchers'
principal outcome, the discontinuation rate. The authors also noted
the apparent superior efficacy of olanzapine to the other drugs
for greater reduction in psychopathology, longer duration of successful
treatment, and lower rate of hospitalizations for an exacerbation
of schizophrenia. In contrast, no other atypical studied (risperidone,
quetiapine, and ziprasidone) did better than the typical perphenazine
on those measures. Olanzapine, however, was associated with relatively
severe metabolic effects: subjects with olanzapine showed a major
weight gain problem and increases in glucose, cholesterol, and triglycerides.
The average weight gain (1.1 kg/month, or 44 pounds for the 18 months
that lasted the study) casts serious doubt on the potentiality of
long-term use of this drug. Perphenazine did not create more extrapyramidal
side-effect as measured by rating scales (a result supported by
a meta-analysis by Dr. Leucht published in Lancet), although more
patients discontinued perphenazine owing to extrapyramidal effects
compared to the atypical agents (8 percent vs. 2 percent to 4 percent,
A phase 2 part of this study roughly replicated
these findings. This phase consisted on a second randomization
of the patients who discontinuated the taking of medication in the
first phase. Olanzapine was again the only medication to stand out
in the outcome measures, although the results did not always reach
statistical significance, in part to the decrease of power. Perphenazine
again did not create more extrapyramidal effects.
A subsequent phase was conducted.  This phase
innovated in allowing clinicians to offer clozapine. Clozapine indeed
proved to be more effective at reducing medication drop-outs than
other neuroleptic agents. Researchers also observed a trend showing
clozapine with a greater reduction of symptoms. However, the potential
of clozapine to cause toxic side effects, including agranulocytosis,
limits the prescription to persons with schizophrenia.
basic principles for medication as an Autism intervention
If you decide to allow medication for your child,
it can pay to not tell others. For example, a teacher may notice
an improvement in behavior without being influenced by knowledge
of the medication being used. Other interventions should not be
changed at this time, so that you can tell if changes are due to
Medications should be introduced carefully, as
the nervous system in many people with Autism is very sensitive
and only a low dose of medication may be needed. Medication trials
should always start with the lowest possible dose, with gradual
increases until its effectiveness is established. The timing of
medication is very important so parents must have a clear understanding
of when it should be taken.
It can be useful to keep a diary of your child's
response to medication, especially if several medications are prescribed.
Don't stop medications abruptly, particularly if they have been
taken for a long time. Always check with your doctor on the best
way to discontinue a prescribed medication if its benefits do not
outweigh its risks.
A 'baseline' should be set before using medication.
These means getting an accurate idea of symptoms so that you can
assess how well the medication is working e.g. how often is the
child having seizures, or violent outbursts, or how many hours sleep
each night. Where possible, this should be written down before,
during, and after using a medication trial.
A child with Autism or Asperger's syndrome may
not respond in the same way to medications as other children. Ideally
parents should work with a doctor who has experience with Autism
Learn about the possible side effects of the
medication and monitor your child closely for their signs.
autistic adults and medication
Many autistic adults themselves are against the
over prescription of neuroleptic drugs in autistic people to control
behavior. Others with co-morbid disorders have been relieved to
have medication to manage these problems. Some psychiatrists are
just now beginning to explore minimal doses of medication for autistic
children. People against the use of Neuroleptic medications for
people with Autism have formed an organization called Autistic People
Against Neuroleptic Abuse.
1. ^ Swainston, Harrison T.; Perry, C.M. (2004).
"Aripiprazole: a review of its use in schizophrenia and schizoaffective
disorder.". Drugs 64 (15): 1715-1736. Retrieved on 2007-11-08.PMID
2. ^ Zuardi, A.W; J.A.S. Crippa, J.E.C. Hallak, F.A. Moreira, F.S.
Guimarães (2006). "Cannabidiol as an antipsychotic drug".
Brazilian Journal of Medical and Biological Research 39: 421-429.
ISSN 0100-879X ISSN 0100-879X.
3. ^ BBC NEWS, Schizophrenia trials 'promising'
4. ^ Murphy, B.P.; Chung YC, Park TW, McGorry PD (12 2006). "Pharmacological
treatment of primary negative symptoms in schizophrenia: a systematic
review". Schizophrenia Research 88 (1-3): 5-25. Retrieved on
5. ^ Photos and videos of tardive dyskinesia can be seen here.
6. ^ American Psychiatric Association (2004) Practice Guideline
for the Treatment of Patients With Schizophrenia. Second Edition.
7. ^ The Royal College of Psychiatrists & The British Psychological
Society (2003). Schizophrenia. Full national clinical guideline
on core interventions in primary and secondary care (PDF). London:
Gaskell and the British Psychological Society.
8. ^ Patrick V, Levin E, Schleifer S. (2005) Antipsychotic polypharmacy:
is there evidence for its use? J Psychiatr Pract. 2005 Jul;11(4):248-57.
9. ^ Jablensky A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper
J, Day R, Bertelsen A. "Schizophrenia: manifestations, incidence
and course in different cultures. A World Health Organization ten-country
study". Psychol Med Monogr Suppl 20: 1-97. PMID 1565705.
10. ^ Hopper K, Wanderling J (2000). Revisiting the developed versus
developing country distinction in course and outcome in schizophrenia:
results from ISoS, the WHO collaborative followup project. International
Study of Schizophrenia. Schizophrenia Bulletin, 26 (4), 835–46.
11. ^ Moncrieff J. (2006) Does antipsychotic withdrawal provoke
psychosis? Review of the literature on rapid onset psychosis (supersensitivity
psychosis) and withdrawal-related relapse. Acta Psychiatr Scand.
Jul;114(1):3-13. PMID 16774655
12. ^ Harrow M, Jobe TH. (2007) Factors involved in outcome and
recovery in schizophrenia patients not on antipsychotic medications:
a 15-year multifollow-up study. J Nerv Ment Dis. May;195(5):406-14.
13. ^ Whitaker R. (2004) The case against antipsychotic drugs: a
50-year record of doing more harm than good. Med Hypotheses. 2004;62(1):5-13.
14. ^ Prien R, Levine J, Switalski R (1971). "Discontinuation
of chemotherapy for chronic schizophrenics". Hosp Community
Psychiatry 22 (1): 4-7. PMID 4992967.
15. ^ Lieberman J et al (2005). "Effectiveness of antipsychotic
drugs in patients with chronic schizophrenia". N Engl J Med
353 (12): 1209-23. PMID 16172203.
16. ^ Stroup T et al (2006). "Effectiveness of olanzapine,
quetiapine, risperidone, and ziprasidone in patients with chronic
schizophrenia following discontinuation of a previous atypical antipsychotic".
Am J Psychiatry 163 (4): 611-22. PMID 16585435.
17. ^ McEvoy J et al (2006). "Effectiveness of clozapine versus
olanzapine, quetiapine, and risperidone in patients with chronic
schizophrenia who did not respond to prior atypical antipsychotic
treatment". Am J Psychiatry 163 (4): 600-10. PMID 16585434.
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