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Psychopharmacology
Psychopharmacology is the study of how psychotropic medications affect psychiatric symptoms, including
thoughts, emotions, and behaviour.
Psychotropic medications, prescribed after careful diagnosis and analysis of symptoms, are widely used to
treat a variety of mental health conditions. These drugs are sometimes referred to as psychoactive (means,
“mind-altering”) medications, indicating that their major effects are on the brain.
While other medications work by enhancing message transmission, while others block communication
between neurons.
Many African Americans metabolize antidepressant and antipsychotic medications more slowly than
European Americans do. What this means is that African Americans sometimes show a more rapid and
greater response to these medications but also experience more side effects.
Caution
Importance of discipline
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Table of psychoactive drugs and their mechanism
Antipsychotics
Mood stabilizers
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Antipsychotic Drugs
Antipsychotic drugs (also called neuroleptics) are used to treat psychotic disorders such as schizophrenia.
Therapeutic benefit of antipsychotics derives from their ability to alleviate or reduce the intensity of
delusions and hallucinations. They do this by blocking dopamine receptors.
These drugs are also useful in treating other disorders with psychotic symptoms such as mania,
psychotic depression, and schizoaffective disorder.
Occasionally used to treat transient psychotic symptoms when these occur in people with borderline
personality disorder and schizotypal personality disorder.
Sometimes used to treat the delusions, hallucinations, paranoia, and agitation that can occur with
Alzheimer’s disease.
However, antipsychotic medications pose great risks to patients with dementia because they are
associated with increased rates of death.
•Chlorpomazine
First-Generation (Low Potency)
•Thioridazine
•Fluphenazine
•Haloperidol Conventional
•Loxapine
•Pimozide
First-Generation (High Potency)
•Prochlorperazine
•Thiothixene
•Trifluoperazine
•Aripiprazole
•Asenapine
•Clozapine
Second Generation •Iloperidone Atypical
•Lurasidone
•Olanzapine
•Quetiapine
Dosage
However, some patients are not able to remember to take their medications each day. In such cases, depot
neuroleptics are used which are basically injected that can last for a longer period of time.
Side effects
One problematic side effect that can result from treatment with conventional antipsychotic medications such
as chlorpromazine is Tardive Dyskinesia.
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This means that the side effect will result in movement related abnormality after taking anti-psychotic
medications. Tardive (from tardy)
Movement related side effects are less common with atypical antipsychotic medications- Clozapine
(Clorazil) & Olanzapine (Zyprexa), mostly preferred in managing schizophrenia. Clozapine also seems to be
especially beneficial for patients with psychosis who are at high risk of suicide.
Due to these side effects clozapine is only used when other drugs have proved to be ineffective.
Atypical antipsychotics (excluding clozapine) are the first-choice treatments for psychosis.
Clozapine and conventional antipsychotics are best considered as second-line therapies.
Anti-depressant drugs
Antidepressants are the most commonly prescribed psychiatric medications. 90% with depressive disorders
are given these medications.
Monoamine oxidase inhibitors [MAOIs] and tricyclic antidepressants [TCAs]) have now been
replaced in routine clinical practice by “second-generation” treatments such as the SSRIs.
In 1988 fluoxetine (Prozac) became the first SSRI to be released in the United States. It is realted to
sertraline (Zoloft) and paroxetine (Paxil).
More recent additions to the SSRI family are fluvoxamine (Luvox), which is used in the treatment of
OCD; citalopram (Celexa); and escitalopram (Lexapro).
Working
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After serotonin being released into the
synaptic cleft, it binds to receptors on the
postsynaptic neuron. A serotonin reuptake
transporter then returns it to the
presynaptic neuron.
Popularity of SSRI
SNRI
Serotonin and norepinephrine reuptake inhibitors (SNRIs) have been introduced recently.
Examples of antidepressants in this drug family are venlafaxine (Effexor) and duloxetine
(Cymbalta).
Side effects: They have similar side effects to the SSRIs but are safe in case of overdose.
Usage: SNRIs seem to help patients who have not responded well to other antidepressants, and they are
slightly more effective than SSRIs in the treatment of major depression.
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Treatment duration
Clinical trials with the SSRIs indicate that patients tend to improve after about 3 to 5 weeks of treatment.
Patients who show at least a 50 percent When treatment removes all of a patient’s
improvement in their symptoms are symptoms, patients are in a period of
considered to have had a positive response remission-if sustained for 6 to 12 months or
to treatment- Better but are not fully well. more, the patient is considered to have
recovered.
Although SSRIs help many people, some people have side effects that are so extreme that they are unable to
continue to take their medication as prescribed.
Not used as frequently used now MAOIs were the first antidepressant medications to be developed
(1950).
Initially were being studied for the treatment of tuberculosis but found evidence of elevated moods in
patients. They were later shown to be effective in treating depression.
Monoamine oxidase inhibitors include isocarboxazid (Marplan), phenelzine (Nardil),
tranylcypromine (Parnate), and selegiline (Eldepryl).
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Working: They inhibit the activity of monoamine oxidase, an enzyme present in the synaptic cleft that helps
break down the monoamine neurotransmitters (such as serotonin and norepinephrine).
Caution: Patients taking MAOIs must avoid foods rich in the amino acid tyramine
Usage: MAOIs are used in certain cases of atypical depression that are characterized by hypersomnia and
overeating and do not respond well to other classes of antidepressant medication.
Tricyclic Antidepressants
First TCA which contained imipramine was being studied as a possible treatment for schizophrenia
when it was found to elevate mood.
Working: The TCAs operate to inhibit the reuptake of norepinephrine and (to a lesser extent) serotonin once
these have been released into the synapse. When the tricyclics are taken for several weeks, they alter a
number of other aspects of cellular functioning including how receptors function and how cells respond to
the activation of receptors and the synthesis of neurotransmitters.
Other Antidepressants
Trazodone
Trazodone (Desyrel) was the first antidepressant to be introduced in the United States that was not
lethal when taken in overdose.
Working: It specifically inhibits the reuptake of serotonin.
Disadvantage: Trazodone has heavy sedating properties that limit its usefulness.
Use: sometimes prescribed with SSRIs to reverse effects on sleep.
Side effect: In rare cases, it can produce a condition in men called priapism- prolonged erection in the
absence of any sexual stimulation
Bupropion
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Other uses of anti-depressant medications (treating other disorders)
SSRIs are often used in the treatment of panic disorder, social phobia, and generalized anxiety
disorder, as well as OCD.
However, some people with panic disorder are greatly bothered by the side effects of these drugs, so
they quickly discontinue the medication.
SSRIs and TCAs are also used in the treatment of bulimia nervosa. These antidepressants are useful
in reducing binge eating and purging.
SSRIs help in mood stability of patients with Cluster B personality disorders such as borderline
personality disorder.
Review of anti-depressants
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Anti- anxiety drugs
Antianxiety drugs are used for conditions in which tension and anxiety are significant components.
They do not provide a cure. However, these medications can keep symptoms under control until
patients are able to receive other forms of effective psychological treatments.
Concerns include the drugs’ addictive potential and sedating effects.
They are often used as supplementary treatments in certain neurological disorders to control
symptoms such as convulsive seizures.
Benzodiazepines
The most important and widely used class of antianxiety (or anxiolytic) drugs are the
benzodiazepines.
Usage of class of drug: the barbiturates (e.g., phenobarbital), is seldom used today except to control
seizures or as anesthetics during electroconvulsive therapy.
The first benzodiazepines were released in the early 1960s. They are now the drugs of choice for the
treatment of acute anxiety and agitation.
Working: work by enhancing the activity of GABA receptors. GABA (gamma amino butyric acid) is an
inhibitory neurotransmitter that plays an important role in the way our brain inhibits anxiety in stressful
situations. The benzodiazepines appear to enhance GABA activity in certain parts of the brain known to be
implicated in anxiety such as the limbic system.
Advantage: They are rapidly absorbed from the digestive tract and start to work very quickly
Uses:-
Caution:
1. Due to their sleep inducing properties people taking these medications are cautioned about driving or
operating machinery.
2. Patients taking these medications must be “weaned” from them gradually because of the risk of
withdrawal symptoms, which include seizures in some cases.
Side effects:
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Other Antianxiety Medications
Buspar
New class released in 1960s is buspirone (Buspar), which is completely unrelated to the
benzodiazepines. Working: thought to act in complex ways on serotonergic functioning rather than
on GABA.
Uses: It has been shown to be as effective as the benzodiazepines in treating generalized anxiety
disorder. Caution: patients who have previously taken benzodiazepines tend not to respond as well
as patients who have never taken them.
Advantage: low potential for abuse, it has no sedative or muscle-relaxing properties. It also does not
cause any withdrawal effects.
Disadvantage: The primary drawback to the use of buspirone is that it takes 2 to 4 weeks to exert
any anxiolytic effects. It is therefore not useful in acute situations. Because it is non-sedating, it
cannot be used to treat insomnia.
John Cade in 1940s discovered that lithium salts such as lithium carbonate were effective in treating
manic disorders.
Around 1970, about 20 years later, lithium treatment was introduced in the United States.
Reasons for delay in its introduction:-
1. Lithium was previously used as a salt substitute for hypertension patients- before its toxiv effects
were known- tragic deaths took place so the medical community refused its usage.
2. It is a naturally occurring compound that makes it not patentable. This meant that drug companies
did not find it profitable to investigate its effects.
Uses:
1. It is widely used for the treatment of bipolar disorder and is marketed as Eskalith and Lithobid.
2. Lithium sometimes relieves depression, although probably mainly in patients with bipolar depression
Evidence of effectiveness: As many as 70 to 80 percent of patients in a clear manic state show marked
improvement after 2 to 3 weeks of taking lithium (Keck & McElroy, 2002). In addition, (Stahl, 2000).
Less effective in long run: There is increasing evidence that lithium maintenance treatment may be less
reliable at preventing future episodes of mania. For example, several studies of patients with bipolar disorder
maintained on lithium for 5 years or more found that only just over one-third remained in remission.
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Relapse: discontinuation of lithium is also very risky. The probability of relapse is estimated to be 28 times
higher after withdrawal than when the patient is on lithium, with about 50 percent relapsing within 6
months.
Side effects
increased thirst,
gastrointestinal difficulties,
weight gain,
tremor
Fatigue.
Lithium can be toxic if the recommended dose is exceeded or if the kidneys fail to excrete it from the
body at a normal rate. Lithium toxicity is a serious medical condition. If not treated swiftly and
appropriately, it can cause neuronal damage or even death.
Patients stop taking the drug: not all patients with bipolar disorder take it exactly as prescribed. Many seem
to miss the “highs” and the abundance of energy associated with their hypomanic episodes, so when faced
with unpleasant side effects and the loss of these highs they may stop taking the drug.
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Anticonvulsants (other drugs to treat mood disorders)
Uses:-
1. Gabapentin (Neurontin), lamotrigine (Lamictal), and topiramate (Topamax) are used for rapid
cycling bipolar disorders.
2. Many of these drugs are also used in the treatment of epilepsy and are anticonvulsant agents.
3. Abilify, an antipsychotic medication, is also now being marketed as a treatment for bipolar disorder.
Side effects:
1. Carbamazepine has been associated with significant side effects including blood problems, hepatitis,
and serious skin conditions.
2. Valproate probably has the fewest and mildest side effects, which can include nausea, diarrhea,
sedation, tremor, and weight gain
Psychotherapy attempts to change the brain by modifying a person’s environment and experience
whereas all of the biological changes the medications try to change the brain by introducing
chemicals into the brain.
Another type of biological intervention uses a third approach—changing the activity of the brain
directly by using electrical activity and/or surgery.
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Ladislas von Meduna, a Hungarian physician, originator of modern ECT. She noted that schizophrenia
rarely occurred in people with epilepsy.
The assumptions: This observation caused him to infer that schizophrenia and epilepsy were somehow
incompatible and to speculate that one might be able to cure schizophrenia by inducing convulsions.
The aim was then to cause such convulsions, they tried doing so through the following techniques:-
Early treatment
Meduna used camphor to induce convulsions in a patient with schizophrenia, who relatively quickly
regained lucidity after the convulsive therapy.
Later, von Meduna began to use a drug called Metrazol to induce convulsions because it operated
more rapidly than camphor.
Adopted by Manfred Sakel, intended to cause convulsions by injecting patients with insulin.
However, these chemical methods gave physicians no control over the induction and timing of the
seizures.
Italian physicians Ugo Cerletti and Lucio Bini tried passing an electric current through a patient’s
head.
This method, which became known as electroconvulsive therapy (ECT), is still used today. In the
United States, about 100,000 patients are treated with ECT each year
Issue of consent: malpractices can be a result of failure to obtain appropriate patient consent, which can be
very difficult when patients may not be legally competent to give such consent due to their illness.
Uses:
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6. Note: Properly administered, ECT is not thought to cause structural damage to the brain
Working: Every neurotransmitter system is affected by ECT, and ECT is known to down regulate the
receptors for norepinephrine, increasing the functional availability of this neurotransmitter. Exact
working of ECT is not clear.
Administration:-
1. In bilateral ECT, electrodes are placed on either side of the patient’s head then they are given a
brief constant-current electrical pulses of either high or low intensity are passed from one side of
the head to the other for up to about 1.5 seconds.
2. In contrast, unilateral ECT involves limiting current flow to one side of the brain, typically the
non-dominant side (right side, for most people). Now people only experience a small twitch of
the hand when the convulsions occur.
Caution:
Unilateral placement
Bite block
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After treatment: After the session is over, the patient has amnesia for the period immediately preceding the
therapy and is usually somewhat confused for the next hour or so.
Treatment duration
Normally, a treatment series consists of fewer than a dozen sessions, more are required.
Treatments are usually administered two or three times per week
Side effects:
1. Bilateral ECT is also associated with more severe cognitive side effects and memory problems than
unilateral.
2. Patients often have difficulty forming new memories (anterograde amnesia) for about 3 months after
ECT ends.
Caution: in prescribing treatment physicians must weigh the greater clinical benefits of bilateral ECT
against its tendency to cause greater cognitive side effects.
Empirical evidence suggests that bilateral ECT is more effective than unilateral ECT. Bilateral although
cause more cognitive side effects.
Some clinicians recommend starting with unilateral ECT and switching to bilateral after five or six
treatments if no improvement is seen.
Another approach using electricity to change brain functioning is Transcranial magnetic stimulation (TMS).
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Working:
TMS is a treatment in which the clinician positions a pulsed magnet over a carefully selected area of
the patient’s scalp and uses it to create an electrical field that increases or decreases neuronal activity
in the brain.
Technological advances have led to the ability to carefully control the location, intensity, frequency,
and pattern of the electrical currents directed at very specific parts of the brain.
Uses: TMS can be used to effectively treat major depression, with additional evidence supporting its use
with other conditions.
Advantage: TMS is less invasive than surgical interventions and has fewer and less severe side effects than
ECT. There are no impairments in memory or concentrations there are with ECT.
Side effects: common side effects from repeated TMS sessions are mild headache and a small risk of seizure.
Effectiveness: Although TMS has shown effectiveness for treating depression and other conditions, it is still
a very new approach and typically is only considered after several courses of psychotherapy and
antidepressant medication have proven ineffective.
Neurosurgery
In 1935 in Portugal, Antonio Moniz introduced a neurosurgical procedure in which the frontal lobes
of the brain were severed from the deeper centres underlying them.
This technique eventually evolved into an operation known as prefrontal lobotomy.
The introduction of the major antipsychotic drugs caused an immediate decrease in the widespread
use of psychosurgery, especially prefrontal lobotomy
Reporting after usage: Initial reports of results tended to be enthusiastic, downplaying complications (which
included a 1 to 4 percent death rate) and undesirable side effects.
Side effects: It was eventually recognized, however, that the side effects of psychosurgery could be very
undesirable indeed.
Used when: used only as a last resort for patients who have not responded to any other form of treatment for
a period of 5 years and who are experiencing extreme and disabling symptoms.
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Working: Modern surgical techniques involve the selective destruction of minute areas of the brain.
1. It involves surgery but does not result in a permanent lesion being made in the brain.
2. It is used to help patients get some relief from their unrelenting symptoms of depression.
Such approaches carry serious risks. Especially when they are concerned with changing the structure of the
brain.
Example: - In one study, 25 patients who had received brain lesions to treat severe OCD were followed up
an average of 11 years later. They had 2 different outcomes for different people.
12/25- Patient’s experienced significant relief from their OCD symptoms after the surgery.
10/25- They showed clinical improvement but also showed evidence of frontal lobe dysfunction.
These included impaired executive functioning on cognitive tests, problems with apathy, and
disinhibited behaviour.
These results highlight the risks of brain surgery even when it is effective in treating the symptoms of
OCD.
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Use of Psychotropic medications (combined treatments)
The treatment of clients with psychotherapy and medication simultaneously is a common practice
throughout the world. Typically, psychosocial interventions are combined with psychiatric medications. This
may be especially beneficial for patients with severe disorders (see Gabbard & Kay, 2001).
Hollon and Fawcett (1995) have noted, “Pharmacotherapy appears to provide rapid, reliable relief from
acute distress, and psychotherapy appears to provide broad and enduring change, with combined treatment
retaining the specific benefits of each.”
Most mental health professionals regardless of disciplines, emphasise the importance of psychotropic
medication, in conjunction with psychotherapy. In fact, psychotherapy and pharmacotherapy are
complementary to each other from various perspectives. For example,
Pharmacotherapy can make amenable for psychotherapy. A client in severe depressive or anxiety
state may not show interest in psychotherapy; however, after some improvement with medication
they can reach a stage where psychotherapy can be started as they become amenable to discuss their
problems.
Medication can increase self-esteem by decreasing feeling of hopelessness, futility and passivity as
well as enhancing the acceptability of treatment.
Medication, for some clients works as placebo effect allowing more substantial therapeutic alliance.
Medication may not only increase the likelihood but also the speed and magnitude of response to
psychotherapy.
On the other hand psychotherapy when added to an ongoing pharmacotherapy may have following
benefits:
– Psychotherapy promotes improved adaption and coping.
– Psychotherapy improves compliance with pharmacotherapy.
– Psychotherapy, even in clients with most severe disorder, decreases the likelihood of recurrence of
symptoms.
– Psychotherapy decreases relapses when medications are stopped.
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Review and extra information
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Overview of Management of Anxiety Disorders
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