Psychopharmacology

D. Olanzapine

Olanzapine (D) is an atypical or second-generation antipsychotic. These
drugs are the usual first line choice for treating psychotic illnesses
such as schizophrenia and generally cause fewer extrapyramidal side
effects compared to older antipsychotic drugs. However, they are not
without side effects and most are associated with weight gain and
metabolic changes. Chlorpromazine (A) is an example of a ‘typical’ or
first-generation antipsychotic, and in fact was the first drug specifically
designed with antipsychotic properties. It is an antagonist at a wide
range of receptors which accounts for some of the side effects observed
with this drug. It has particularly potent anticholinergic effects. Isoniazid
(B) is an anti-tuberculous agent which has incidental antidepressant
activity. Lithium carbonate (C) is an inorganic ion that has antimanic
properties as well as being used in the prophylaxis of bipolar disorder.
Trazodone (E) is an antidepressant in the ‘SARI’ (serotonin antagonist
and reuptake inhibitor) class. It also has prominent sedative and
anxiolytic properties.

D. Serotonin and noradrenaline reuptake inhibitor (SNRI)

Venlafaxine (D) is an SNRI. It is used as a second line agent for treating
depression. Monoamine oxidase inhibitors (A) are another class of
antidepressants. They are seldom used in current practice because of
their side effect profile as well as potential interaction with various
tyramine-rich foods (commonly referred to as the ‘cheese reaction’).
Noradrenaline (or norepinephrine) reuptake inhibitors (NARIs) (B)
include atomoxetine and reboxetine, also developed for the treatment
of depression. SSRIs (C) are now the most commonly used class of
antidepressants and include agents such as fluoxetine, sertraline and
citalopram. They are generally well tolerated and are less lethal in
overdose compared with older drugs. Tetracyclic antidepressants (E)
include mirtazapine and mianserin.

E. Trimipramine

Trimipramine (E) is a tricyclic antidepressant. Antidepressants must
be used cautiously in patients with bipolar affective disorder as there
is a risk of inducing a manic episode, although they are sometimes
necessary in patients with depressive episodes as part of their bipolar
disorder. Carbamazepine (A), lamotrigine (B) and sodium valproate (D)
are all anti-epileptic agents used in the prophylaxis of bipolar disorder
as well as the acute manic phase of the illness, although lamotrigine is
thought to be more effective in treating depressive episodes than mania.
Lithium carbonate (C) is an inorganic ion used in the treatment of mania,
depression and the prophylaxis of bipolar disorder.

D. Quetiapine

Quetiapine (D) is an atypical, or second-generation, antipsychotic, which
are recommended by NICE as first line agents in new-onset schizophrenia.
There have been increasing concerns about these agents in terms of their
metabolic side effects, and as a result there has been some resurgence in
the use of older, typical antipsychotic drugs. Clozapine (A) is a powerful
antipsychotic that is reserved for the treatment of treatment-resistant
schizophrenia. It is associated with a significant risk of developing
neutropenia or even agranulocytosis, which means the patient must have
regular full blood count checks. Lithium carbonate (B) is used in bipolar
disorder and affective psychoses, not typically in schizophrenia. Pimozide
(C) is an older antipsychotic that is used very infrequently in current
practice. It has been associated with unexplained deaths and should only be
prescribed after an electrocardiogram (ECG). Regular monitoring with ECG
is also recommended during treatment. It is associated with prolongation of
the QT interval and should not be used with other drugs (such as tricyclic
antidepressants) that may also prolong the QT, or with drugs that may
cause electrolyte disturbances such as diuretics. Sertraline (E) is an SSRI
used as an antidepressant. It does not have antipsychotic properties.

B. Diazepam

Diazepam (B) is a benzodiazepine with various indications, such as relief
of anxiety and as a sedative. It, like all the benzodiazepines, is associated
with the development of tolerance and possible dependence so should
only be used in short-term management. It does not have antimanic
properties as such, but is often used to control agitation and other erratic
behaviours during an acute manic episode. Carbamazepine (A) and sodium
valproate (E) are both anti-epileptics used in the prophylaxis of bipolar
disorder. Lithium (C) is an inorganic ion used in the treatment of mania,
depression and the prophylaxis of bipolar disorder. Olanzapine (D) is an
antipsychotic that is also effective in (and licensed for) the prophylaxis
of bipolar disorder.

B. Haloperidol

Delirium is treated in various ways, and certainly not just pharmacologically.
While in certain circumstances benzodiazepines may be used, generally
an antipsychotic is the treatment of choice, such as haloperidol (B).
Amitriptyline (A) is a tricyclic antidepressant. Given its anticholinergic
properties it may actually worsen confusion and would therefore not be
an appropriate choice. Lithium carbonate (C) is used for the prophylaxis
of bipolar disorder and treatment of manic and depressive episodes. It
does not have a role in the treatment of delirium. Temazepam (D) is
a benzodiazepine and also a controlled drug. As stated above, while
on some occasions benzodiazepines may be an appropriate choice for
treatment of delirium, temazepam would not be the most appropriate one
to choose from this class. A rare but important consequence of the use
of benzodiazepines is paradoxical agitation. Zuclopenthixol acetate (E),
trade name Acuphase, is a potent intramuscular antipsychotic medication.
It is used in the management of extremely agitated patients who are
not responding to the standard pharmacological treatments for rapid
tranquilization. It should be used with extreme caution, only in specialist
units and for short-term management.

C. Flupentixol decanoate

Tardive dyskinesia is a distressing complication of antipsychotic use. It
typically comes on after many years of treatment (hence ‘tardive’) and
is associated principally with the use of typical antipsychotic agents,
and in particular depot medications, such as flupentixol decanoate (C).
It is extremely difficult to treat once present. Aripiprazole (A) is a
newer antipsychotic which appears to have a lower incidence of tardive
dyskinesia than older agents (although of note it has not been licensed
for a sufficient length of time to definitively state this). Clozapine (B) is
a potent antipsychotic used in the management of treatment-resistant
schizophrenia. Unlike other agents, it is actually thought to improve the
symptoms of tardive dyskinesia. Lithium carbonate (D), an antimanic agent,
and trazodone (E), an antidepressant, rarely cause tardive dyskinesia.

D. Donepezil

Donepezil (D) is an acetylcholinesterase inhibitor (AChEI), used to ameliorate
the cognitive and non-cognitive symptoms of dementia. It works by increasing
the functional amount of acetylcholine in the brain. Aripiprazole (A) is an
antipsychotic that works as a partial dopamine agonist. Carbamazepine (B)
is an anti-epileptic with mood stabilizing qualities. Diazepam (C) is a
benzodiazepine. These drugs work as GABA agonists. Haloperidol (E) is
another antipsychotic. It is thought to exert its antipsychotic effects by, as
with other antipsychotic drugs, antagonizing dopamine.

D. Procyclidine

Procyclidine (D) is an antimuscarinic (anticholinergic) agent used in
Parkinson’s disease as well as to treat the parkinsonian (extrapyramidal)
side effects of antipsychotic medication. Myaesthenia gravis (MG) is an
autoimmune neurological disorder caused by circulating antibodies against
acetylcholine receptors at the postsynaptic neuromuscular junction. Any
drugs that inhibit acetylcholine (such as anticholinergics) will worsen the
symptoms of MG. Chlorpromazine (A) is a first-generation antipsychotic.
It should be used with caution in patients with MG as it does have
anticholinergic properties. However, it is not contraindicated as such.
Citalopram (B) is an SSRI. It has potent effects at the 5-HT1A receptor but
minimal activity at muscarinic receptors (although note not zero activity).
Galantamine (C) is an AChEI used in the management of Alzheimer’s disease.
It increases the availability of acetylcholine so in theory should improve the
symptoms of MG, although it does not have a license for this in the UK.
Pyridostigmine (E) is another AChEI, but in this case is used in the treatment
of MG and in fact is one of the mainstays of treatment.