1. Bailee Coy
Dr. Corina Brown
CHEM 381-004
November 30th
, 2015
Tardive Dyskinesia
Abstract
All prescription medications come with the risk of developing side effects or having
undesirable reactions, but taking a prescription medication for a long period of time
comes with the risk of those side effects and reactions being very severe and
sometimes even life threatening. Specifically talked about in this paper is the severe
side effect to an antipsychotic used for the treatment of schizophrenia. This side effect
is Tardive Dyskinesia; it is an uncontrollable movement disorder usually affecting the
oral and facial regions of the patient due to prolonged use of an antipsychotic. There are
two types of antipsychotics, typical and atypical. Both types are used for treating
schizophrenia, and both have a high risk of developing Tardive Dyskinesia. A very
severe and very uncommon disorder, Tardive Dyskinesia does not affect every patient
taking an antipsychotic even if taken for a long period of time. Pathophysiology for this
disorder is not well understood, so when an antipsychotic is prescribed careful and
close monitoring must be done to insure the patient is safe and not developing any
symptoms of Tardive Dyskinesia. At this point in time there is no cure for Tardive
Dyskinesia and with the lack of understanding of this disorder the chances for a future
cure are very slim.
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2. Introduction
When taking a prescribed medication for a long period of time many side effects
and/or issues may arise, specifically with the chronic use of an antipsychotic.
Antipsychotics are used for the treatment of schizophrenia and other mood disorders
(Wu et al., 2013). Two types of antipsychotics exist, typical and atypical. Typical
antipsychotics function by only blocking dopamine (neurotransmitter) within the patient,
whereas atypical antipsychotics block dopamine while also affecting the serotonin level
of the patient (“Antipsychotics,” n.d.). Usually atypical antipsychotics are chosen for the
treatment of schizophrenia, however typical antipsychotics can be used. When requiring
treatment with an antipsychotic there is the concern of serious side effect risks for the
patient. One very severe yet very rare side effect developed from long-term use of
antipsychotics is Tardive Dyskinesia (Bassett et al., 1986; Cho and Lee, 2013; Coplan
et al., 2013; Dolder and Jeste, 2003; Wu et al., 2014;). After several months or even
years of antipsychotic use Tardive Dyskinesia begins to develop and symptoms will
occur in the patient (Bassett et al., 1986). Some of which are uncontrollable oral and
facial movements and in more severe cases the extremities may also move
uncontrollably (Bassett et al., 1986; Catherine and Lang, 2014; Gardos et al., 1977; Wei
et al., 2012). This paper will review background information about Tardive Dyskinesia,
what causes Tardive Dyskinesia in biochemistry terms, and how it is treated if at all
possible.
Body
Tardive Dyskinesia (TD) is a late appearing movement disorder characterized by
uncontrollable oral, facial, and limb movements due to prolonged antipsychotic use
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3. (Bassett et al., 1986; Catherine and Lang, 2014; Gardos et al., 1977; Wei et al., 2012).
If well predicted and caught very early, Tardive Dyskinesia may be reversible at the start
however if not the disorder will progress to be lifelong and is currently untreatable (Cho
and Lee, 2013). When prescribing an antipsychotic it is important for the doctor to
understand the medication, know the higher risk factors, and to always be aware of the
patient’s comments and complaints about the medication. If the medication is causing
undesirable symptoms or changes in the patient it should be stopped immediately. Not
every patient taking an antipsychotic for a long period of time develops Tardive
Dyskinesia (Bassett et al., 1986). However patients that are female and older in age
along with the length of their antipsychotic use are at higher risk of developing Tardive
Dyskinesia (Wei et al., 2012; Wu et al., 2014; Wu et al., 2013). A study performed
between 2004-2008 showed that with the use of an atypical antipsychotic the incidence
of Tardive Dyskinesia was 3.9% annually and with the use of a typical antipsychotic the
incidence was 5.5% annually for patients with schizophrenia (Coplan et al., 2013). In
that study percentages are very low, clearly showing how rare TD really is and how
either typical or atypical antipsychotics can result in the development of this disorder.
When it comes to the pathophysiology for Tardive Dyskinesia, it is not well
understood (Wei et al., 2012; Wu et al., 2014; Wu et al., 2013). However theories
suggest that oxidative stress and the generation of free radicals causes neurotoxicity in
the patient, leading to the development of Tardive Dyskinesia (Catherine and Lang,
2014; Cho and Lee, 2013; Wu et al., 2014; Wu et al., 2013). Relating the development
of Tardive Dyskinesia to biochemistry, when dopamine is blocked for a long period of
time with the use of an antipsychotic, oxygen cannot take its normal route of conversion
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4. to water, therefore a small percentage of oxygen produces a superoxide anion (O2
-
),
hydrogen peroxide (H2O2), or hydroxyl radical (Cho and Lee, 2013). With the production
of O2
-
the intramitochondrial antioxidants must work to prevent oxidative damage,
therefore leading to impairment in ATP production because all forces are turned to
protecting rather than generating (Cho and Lee, 2013). Free radicals (molecules with
unpaired electrons) can be very damaging to the body, so enzymes are used to
catalyze and alter free radicals produced from prolonged use of antipsychotics into non-
radical forms (Cho and Lee, 2013). Researchers have very little understanding for all of
these processes as to why they result from antipsychotics, but it is understood that
when these processes are uncontrolled or stray away from their normal route it leads to
complications for instance the development of TD.
Since Tardive Dyskinesia is so lowly understood, no treatment currently exists
(Catherine and Lang, 2014; Wei et al., 2012). The only hope for treatment of Tardive
Dyskinesia is in the early developing stages. If aware and caught very early on TD may
be reversible for about 1/3 of the patients being affected by it (Bassett et al., 1986;
Emsley et al., 2011). However, once Tardive Dyskinesia has developed its severity can
only get worse and more untreatable. To possibly be reversible the use of
antipsychotics must be stopped immediately, but this can cause other problems for the
patient like increasing the severity of schizophrenia because it is no longer being
treated. Due to the lack of understanding the future for an absolute cure is very slim.
Summary
In this paper the very rare and uncommon side effect Tardive Dyskinesia was
explained and defined. As discussed in this paper the use of antipsychotics (typical or
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5. atypical) for the treatment of Schizophrenia, has the chance of developing Tardive
Dyskinesia. With very little understanding of this condition it is more important to prevent
TD from developing than relying on the chance of reversing its affects. This lifelong
disorder can be very severe, so it is always important to understand and be able to
detect signs before conditions worsen.
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