Antipsychotic as treatment mode for psychotic disorders

Course Title:

Psychophysiology and psychopharmacology II

Submitted to,

Dr. Shazia

Submitted by

Khizra Khurshid (616)

MS Clinical Psychology 2nd semester

Applied Psychology,

Government College University, Faisalabad.

1. Overview

Antipsychotic medications can reduce or relieve symptoms of psychosis, such as delusions

(false beliefs) and hallucinations (seeing or hearing something that is not there). Formerly known
as major tranquilizers and neuroleptics, antipsychotic medications are the main class of drugs
used to treat people with schizophrenia. They are also used to treat people with psychosis that
occurs in bipolar disorder, depression and Alzheimer’s disease. Other uses of antipsychotics
include stabilizing moods in bipolar disorder, reducing anxiety in anxiety disorders and reducing
tics in Tourette syndrome.

Antipsychotic medications can help to calm and clear confusion in a person with acute
psychosis within hours or days, but they can take up to four or six weeks to reach their full
effect. These medications can help to control symptoms, but they do not cure the underlying
condition. When taken over a longer term, antipsychotics can help to prevent further episodes of
psychosis.

While antipsychotic medications can help some people with psychosis and mood disorders,
these drugs can have serious side-effects. The aim of medication treatment is to reduce and
control symptoms while keeping side-effects at a minimum.

Combining antipsychotic medication with other therapy and support can help people to
manage symptoms and improve quality of life. Family therapy, peer support, school and job
counselling, and housing and employment supports can all be helpful. Some therapists now.
Offer cognitive-behavioural therapy to help people cope with voices and other auditory
hallucinations.

Taking care of your physical health is especially important if you take antipsychotic
medication. Both schizophrenia and the medications used to treat it can increase the risk of
diabetes and other serious health problems. Getting regular check-ups and medical care can help
you to have good physical health. Eating a nutritious diet, exercising regularly and getting
enough sleep can also help you to get and stay well.
 Antipsychotics are psychiatric drugs which are available on prescription, and are licensed to
treat types of mental health problems whose symptoms include psychotic experiences. These
include:

 schizophrenia
 schizoaffective disorder
 some forms of bipolar disorder
 severe depression
Some antipsychotics may also be used to treat:

 severe anxiety (but only in very low doses)

 physical problems, such as persistent hiccups, problems with balance and nausea (feeling
sick)
 agitation and psychotic experiences in dementia (although they're not usually
recommended in this case).
1.1. Uses
Antipsychotic drugs don't cure psychosis but they are often effective in reducing and
controlling many symptoms, including:

 delusions and hallucinations, such as paranoia and hearing voices

 anxiety and serious agitation, for example from feeling threatened
 incoherent speech and muddled thinking
 confusion
 violent or disruptive behaviour
 mania
Rather than getting rid of these symptoms completely, the drugs may just stop you feeling so
bothered by them – so you feel more stable and can get on with leading your life the way you
want to.
 1.2. Side effects of Antipsychotic Medications

Antipsychotic medication can cause unpleasant side-effects, especially when the

symptoms are severe and a higher dose of medication is used. Side-effects should become mild
or at least tolerable when the dose is reduced and as your body adjusts to the presence of the
drug.

Most side-effects will go away when you stop taking the drug. There is a risk, however,
of a condition that causes people to make involuntary movements, known as tardive dyskinesia,
which can be permanent.
 Some people accept the side-effects as a trade-off for the relief these drugs can bring.
Others find the side-effects distressing and may choose not to take the medication.

Check the information given to you by your doctor or pharmacist to find out the specific
side-effects of any drug you have been prescribed. If you are troubled by any of these effects, it
is best to continue to take your medication as prescribed and let your doctor know as soon as
possible. Your doctor may:

 adjust your dose

 prescribe other medications to help control side-effects
 change your medication.

1.2.1. Side-effects of antipsychotics

 Movement effects: Tremors, muscle stiffness and tics can occur. The higher the dose, the
more severe these effects. The risk of these effects may be lower with the second-
generation medications than with the older drugs. Other drugs (e.g., benztropine
[Cogentin]) can be used to control the movement effects.
 Dizziness: Feelings of dizziness may occur, especially when getting up from a sitting or
lying position.
 Weight gain: Some of the second-generation drugs are thought to affect people’s sense
of having had enough to eat. They can also be sedating. These two effects can result in
weight gain, which can increase a person’s risk of diabetes and heart disease.
 Diabetes: Schizophrenia is a risk factor for diabetes. Antipsychotic drugs can increase
this risk.
 Agitation and sedation: Some people feel “wired” and unable to stop moving when
taking antipsychotics. This effect may be mistaken for a worsening of illness rather than a
side-effect of the medication. These same drugs can also have the opposite effect, making
people feel tired. Some people may feel either wired or tired, and some may feel both at
the same time.
 Tardive dyskinesia: For every year that a person takes antipsychotic medication, there is
a five per cent chance of developing tardive dyskinesia (TD), a condition that causes
 people to have repetitive involuntary movements. The risk of TD is highest with the first-
generation antipsychotics, although it can occur with the second-generation drugs. TD
can worsen when you stop taking medication and can be permanent.
 Neuroleptic malignant syndrome: This rare but serious complication is usually
associated with the use of high doses of typical antipsychotics early in treatment. Signs
include fever, muscle stiffness and delirium.

Side-effects vary depending on the type of medication. More information on side-effects is

included with each type of antipsychotic. 

1.2.2. Controlling the side-effects of antipsychotics

You can help to control possible side-effects on your own by:

 getting regular exercise and eating a low-fat, low-sugar, high-fibre diet (e.g., bran, fruits
and vegetables) to reduce the risk of diabetes and help prevent weight gain and
constipation
 using sugarless candy or gum, drinking water, and brushing your teeth regularly to
increase salivation and ease dry mouth
 getting up slowly from a sitting or lying position to help prevent dizziness.
 1.3. Effectiveness

1.4. Mechanism

They all reduce dopaminergic neurotransmission. There are two options: the first is through
D2 antagonism, both first- and second-generation antipsychotics can block D2 receptors. The
second option is through partial agonism: at this time the only approved second-generation
antipsychotic is aripiprazole.
 There are 4 pathways key to antipsychotics pharmacology. Blockade of two of these
pathways can lead to adverse effects. The other two pathways are relevant to schizophrenia
symptoms. In this figure the mesolimbic pathway is shown in blue, the dopamine theory
postulates that positive symptoms such as delusions, hallucinations and thought disorder might
be caused by an overactivity of this pathway. In the other figure, the mesocortical pathway is
depicted in red. Recent findings suggest that a dysfunction of the mesocortical pathway may be
part of the neurobiology of negative and cognitive symptoms. So, in review, an excessive
activation of the dopamine mesolimbic pathway is related to positive symptoms, while negative
and cognitive symptoms might be caused by mesocortical dysfunction.
 The dopamine hypothesis of schizophrenia postulates that postsynaptic dopamine
antagonism is the common mechanism that explains antipsychotic properties.
The pharmacologist and clinician Stephen Stahl argue that it would be more appropriate to refer
to this theory as “the dopamine hypothesis of positive symptoms of schizophrenia”. The reason
is that there are more pathways and psychopathological dimensions that are not included in this
theory.

Drug-induced psychosis risk is very high with drugs that increase synaptic dopamine
availability. This includes drugs such as cocaine, amphetamines and L-dopa. In fact, this can be a
potential complication for patients suffering Parkinson’s disease treated with L-dopa.
 Schizophrenia neurobiology is very complex and the dopamine theory has limitations.
The first limitation is that it doesn’t explain cognitive deficits in schizophrenia patients. The
second limitation is that psychotomimetic effects of activation of other pathways are not
included in this theory. For example, d-lysergic acid is a 5-HT2A agonist that can produce
psychotic symptoms.
 Now the mechanism of action of first- and second-generation antipsychotics. First-
generation or conventional antipsychotics are D2 antagonists, they lower dopaminergic
neurotransmission in the four dopamine pathways. In addition, they can also block other
receptors such as histamine-1, muscarinic-1 and alpha-1.

Second-generation antipsychotics are also known as “atypical” antipsychotics. This term

was originally used to refer to a lower risk of extrapyramidal effects for the antipsychotic
clozapine. The other less used term is serotonin-dopamine antagonists, this describes one of their
key features, which is the ability to block serotonin receptors.

The mechanisms of second-generation antipsychotics in four parts. These are the most
accepted theories on how antipsychotic drugs might work. In the next slides we’ll see why
5HT2A antagonism is important.

One of the most important features of second-generation antipsychotics is their 5-HT2A

antagonism. In this slide we’ll use clozapine as an example, this is because this was the first drug
in its group. Clozapine has very high affinity for 5–HT2A receptors, and a lower D2 affinity than
haloperidol. This led researchers such as Herbert Meltzer to propose that the differential
antipsychotic effect of clozapine is related to its high 5-HT2/D2 ratio.
  5HT2A antagonism can increase dopaminergic neurotransmission in the nigrostriatal
pathway, reducing the risk of extrapyramidal symptoms. It could also theoretically improve
negative and cognitive symptoms in schizophrenia by increasing dopamine release in the
prefrontal cortex.

Another theory of “atypicality” proposes that second-generation antipsychotics dissociate

rapidly from D2 receptors, this would be a possible explanation for the lower risk of EPS of
drugs such as clozapine and quetiapine. This table compares first and second-generation
antipsychotics in terms of their binding to D2 receptors. Conventional antipsychotics tend to bind
more “tightly” to dopamine receptors than dopamine itself. Clozapine and the other second-
generation agents bind to D2 receptors more “loosely”, so in the presence of dopamine they tend
to come off the receptor more easily.

This short sequence depicts fast dissociation from D2 receptors. In this image, we can see
the “loose” binding of a second generation agent to the receptor.

 In the presence of dopamine, the drug easily dissociates from the receptor.
Now here we can see how dopamine finally binds the D2 receptor.
 Some second-generation antipsychotics can also bind to 5HT1A receptors. Another
property of second-generation antipsychotics is that some of them are 5HT1A agonists.
This includes drugs such as ziprasidone, quetiapine and clozapine. What is the importance of
this? 5HT1A agonism would increase dopamine release in the prefrontal cortex also reduce
glutamate release.

Antipsychotic action is associated with adaptive modifications that involve changes in

intracellular signal transduction and gene expression in target neurons. These changes appear to
be initiated by binding to dopaminergic, serotonergic, muscarinic, adrenergic and other
receptors. Most of these receptors belong to the G-protein-coupled receptors family.
Downstream effectors include:

 Adenylate cyclase

 Various ion channels

 Phospholipases

 cAMP

 cAMP dependent kinase

 Protein kinase C, Protein lipase C.

We see the relationship between D2 occupancy and risk of extrapyramidal side effects.
PET studies show that D2 receptor occupancy predicts both clinical efficacy and EPS. In this
graphic, we see that occupancies in the range between 60 and 75% are associated with clinical
antipsychotic efficacy. If we increase the antipsychotic dose above a 78% occupancy, there is an
increased risk of extrapyramidal symptoms. In clinical terms, this means that the optimal dosing
of any antipsychotic agent is one that occupies between 60 to 75% of D2 receptors.

1.4.1. Summary:

This table summarizes some core concepts on the mechanism of action of first- and
second-generation antipsychotics. Conventional agents are D2 antagonists, while second-
generation antipsychotics have a high 5-HT2A /D2 ratio. This means that they block more
potently 5-HT2A receptors than D2 receptors. They also show rapid dissociation from D2
receptors, and some of them such as quetiapine, ziprasidone and clozapine have 5-HT11A
agonism. Depending on each individual agent, both first- and second-generation antipsychotics
can block muscarinic-1, histamine-1 and alpha-1 receptors, among others.
2. Categories of antipsychotic

This category of medications falls into two categories:

2.1. Typical Antipsychotics, or First-Generation Antipsychotic Drugs. 

The typical, or conventional, antipsychotics were first developed in the 1950s. Haldol
(haloperidol) and Thorazine (chlorpromazine) are the best-known typical antipsychotics.
They continue to be useful in the treatment of severe psychosis and behavioural problems
when newer medications are ineffective. However, these medications do have a high risk of
side effects, some of which are quite severe. In response to the serious side effects of many
typical antipsychotics, drug manufacturers developed another category referred to as
atypical antipsychotics.

2.2. Atypical Antipsychotics, or Second-Generation Antipsychotic Drugs. 

 These new medications were approved for use in the 1990s. Clozapine, asenapine,
olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and
aripiprazole are atypical antipsychotic drugs. With the discovery of clozapine in 1959, it
became evident that this drug was less likely to produce extrapyramidal effects (physical
symptoms such as tremors, paranoia, anxiety, dystonia, etc. as a result of improper doses or
adverse reactions to this class of drug) in humans at clinically effective doses than some
other types of antipsychotics. Clozapine was categorized as the first atypical antipsychotic
drug. This category of drugs has also been of great value in studying the pathophysiology of
schizophrenia and other psychoses.

2.3. First generation antipsychotics (Typical)

 First-generation antipsychotics (FGAs) are drugs used primarily for the treatment of
schizophrenia and related psychotic disorders. The use of FGAs has declined in the last few
years, mainly because of an increase in prescriptions of second-generation agents. Since FGAs
are considerably less expensive than newer antipsychotics, they remain a valuable option in the
treatment of psychotic disorders.

The first generation of antipsychotics have been prescribed since the 1950s. The following
medications are typical antipsychotics. They have been listed by their generic name with the
brand name in brackets.

 Benperidol (Anquil)
 Chlorpromazine (Largactil)
 Flupentixol (Depixol)
 Fluphenazine (Modecate)
 Haloperidol (Haldol)
 Levomepromazine (Nozinan)
 Pericyazine
 Perphenazine (Fentazin)
 Pimozide (Orap)
 Promazine
 Sulpiride (Dolmatil, Sulpor)
 Trifluoperazine (Stelazine)
 Zuclopenthixol (Clopixol)

Mechanism of Action

The exact mechanism of action of antipsychotic drugs is unknown. According to the

dopamine theory of schizophrenia, positive symptoms are the result of overactivity in the
mesolimbic dopamine pathway. This is in part based on the observation that drugs that increase
dopaminergic availability (L-DOPA, cocaine, amphetamines) can trigger psychotomimetic
effects in individuals not affected by schizophrenia. As the image below shows, first-generation
antipsychotics are D2 antagonists. As a result, they reduce dopaminergic neurotransmission in
the four dopamine pathways.
The implications are the following:

Mesocortical pathway.

Research on schizophrenia pathophysiology suggests that a dysfunction of this pathway

is associated with cognitive impairments and disturbances of emotions and affect (negative
symptoms).  Blockade of the mesocortical pathway by high doses of first-generation
antipsychotics can induce secondary negative symptoms and cognitive effects.

Mesolimbic pathway: Antipsychotic effects

As explained earlier, overactivity of this pathway is thought to be involved in the

pathophysiology of positive symptoms of schizophrenia. Blockade of D2 receptors in the
mesolimbic pathway has been proposed as a possible mechanism of antipsychotic action of first-
generation agents.

Nigrostriatal pathway: Extrapyramidal Symptoms

 Antagonism of D2 receptors in the nigrostriatal pathway is associated with increased risk
of extrapyramidal symptoms.

Tuberoinfundibular pathway: Hyperprolactinemia

Dopamine acts as a prolactin-inhibiting factor, D2 blockade increases prolactin levels by

promoting its release in the pituitary gland.

2.4. Second generation antipsychotics (Atypical)

Antipsychotic drugs are designed to treat a severe psychiatric condition known as psychosis.
Psychosis is characterized by the distortion of thoughts during which a person loses touch with
reality, often manifesting with hallucinations, paranoia, or delusions.

The second generation of antipsychotics have been used more since the 1990s. Although
some of them were developed before then. They have been listed by their generic name with the
brand name in brackets.

 Amisulpride (Solian)
 Aripiprazole (Abilify, Abilify Maintena)
 Clozapine (Clozaril, Denzapine, Zaponex)
 Risperidone (Risperdal & Risperdal Consta)
 Olanzapine (Zyprexa)
 Quetiapine (Seroquel)
 Paliperidone (Invega, Xeplion).

2.5. Clozapine

Clozapine works slightly differently to others. It is sometimes given to people who are
treatment resistant. This means other medication hasn’t helped their symptoms. The National
 Institute for Health and Care Excellence (NICE) says that people with schizophrenia should
only be offered clozapine after having tried 2 other drugs.

Clozapine can cause your white blood cell numbers to drop, but this is rare. This could mean
that you get infections more easily. If you take clozapine, you will need regular blood tests to
make sure your white blood cell count is healthy.

If your white blood cell numbers start dropping, you will be asked to stop taking the
medication. You will have another blood test after you have stopped clozapine to make sure they
are back to normal. Your doctor might decide to change your dose of clozapine or offer you
another type of medication.

Mechanism of action

Atypical clinically help patients by transiently occupying D2 receptors and then rapidly
dissociating to allow normal dopamine neurotransmission. This keeps prolactin levels normal,
spares cognition, and obviates EPS. One theory of atypicality is that the newer drugs block 5-
HT2A receptors at the same time as they block dopamine receptors and that, somehow, this
serotonin-dopamine balance confers atypicality. This, however, is not borne out by the results.
While 5-HT2A receptors are readily blocked at low dosages of most atypical antipsychotic drugs
(with the important exceptions of remoxipride and amisulpride, neither of which is available for
use in Canada) the dosages at which this happens are below those needed to alleviate psychosis.
In fact, the antipsychotic threshold occupancy of D2 for antipsychotic action remains at about
65% for both typical and atypical antipsychotic drugs, regardless of whether 5-HT2A receptors
are blocked or not. At the same time, the antipsychotic threshold occupancy of D2 for eliciting
EPS remains at about 80% for both typical and atypical antipsychotics, regardless of the
occupancy of 5-HT2A receptors. Relevance: The “fast-off-D2” theory, on the other hand,
predicts which antipsychotic compounds will or will not produce EPS and hyperprolactinemia
and which compounds present a relatively low risk for tardive dyskinesia. This theory also
explains why L-dopa psychosis responds to low atypical antipsychotic dosages, and it suggests
various individualized treatment strategies.
3. Effectiveness of typical and atypical psychotics
Categories Atypical
Mechanism of action The atypical antipsychotics
are dopamine antagonists but
also block 5-HT2A receptors.
They block 5-HT to a greater
extent than dopamine. D2
partial a agonist.
POTENCY All atypical antipsychotics
have activity at the 5-HT2A
receptor and dopamine
Typical
The antipsychotic effect of
these medications is primarily
medicated through blockade
of dopamine receptors (D2
antagonists)
Typical antipsychotics agents
are classified by their potency
for the dopamine receptor
 receptor. Different agents
have different activity for
histamine a-, Musca nine
receptors.
EFFICACY Atypical antipsychotics have
increased efficacy for
negative symptoms are
compared to typical
antipsychotics. With the
exceptions od clozapine, all
antipsychotics are thought to
have similar efficacy for
positive symptoms.
Clozapine have demonstrated
efficacy for treatment-
resistant schizophrenia.
into high and low potency
antipsychotics. Low potency
AP have low affinity for
dopamine receptor thus low
EPS.
When do sed in equivalent
doses, the various typical
antipsychotics have similar
efficacy. Equivalent doses are
described using
chlorpromazine (CPZ)
equivalent. Typical
antipsychotics are through to
be as effective as typical
antipsychotics for positive
symptoms but are less for
effective symptoms.

4. General and specific side effect of typical and atypical

People who take antipsychotic medications may experience negative side effects, such as:

 Extrapyramidal Effects: Dystonias, akathisia, tardive dyskinesia, Parkinson’s-like

symptoms, unwanted movements, ataxia, muscle breakdown, rigidity, tremors,
and seizures are some major effects of this category of drugs. Neuroleptic malignant
syndrome may occur as well.
 
 Effects on the Central Nervous System: Drowsiness, sedation, and hypnosis occur.
Confusion, vertigo, syncope, disturbed sleep, nightmares, and agitation are also
reported by various studies. Dementia, amnesia, and loss of memory are some
adverse effects. Suicidal ideation in old and young with increased mania, anxiety,
agitation, violent behaviour, and depression can also be seen in people taking these
 drugs.
 
 Effects on the Cardiovascular System: Cardiomyopathy is noted in nine out of
every 100,000 people using clozapine. Alteration in electrocardiogram (ECG)
readings, chest pain, angina, myocarditis, palpitation, tachycardia, edema, phlebitis,
and arrhythmias are serious adverse effects. Myocardial infarction (heart attack)
occurs in only 1% of people using this category of drug. Orthostatic hypotension—
the medical name for the fuzzy feeling you get when standing up to quickly—is very
common.
 
 Hepatic (Liver) Effects: These agents increase the serum concentration of alkaline
aminotransferase. Reversible liver cell hyperplasia, increase in bilirubin, jaundice,
drug induced hepatitis, and necrosis have been recorded in studies.
 
 Gastrointestinal Effects: Constipation, dry mouth, anorexia, weight gain, increases
in pancreatic enzymes, epigastric distress, abdominal cramps, dyspepsia, heartburn,
and nausea are some common adverse effects.
 
 Genitourinary (Urinary and Reproductive) Effects: Impotence, delayed
and premature ejaculation, testicular swelling, priapism, increased or
decreased libido, virginal itching, enuresis, polyuria, breast engorgement,
galactorrhea, and anorgasmia have been reported.
 
 Other Effects: Cases of blurred vision, hot flashes, dry throat, nasal congestion,
severe hyperglycemia, numbness, chills, glaucoma, leukopenia, neutropenia,
hyperlipidemia, agranulocytosis, and respiratory depression have been reported.
 
 Pregnancy and Lactation: Antipsychotic drugs can be used in pregnant females
since they have shown no teratogenic (development of the fetus or embryo) effects in
animal studies. Drugs like clozapine and olanzapine have shown no harm to the fetus.
 However, during lactation, the metabolites may be disturbed in the milk and could
harm the newborn.

4.1. Specific side effect of atypical antipsychotics

Atypical antipsychotics are more likely than typical antipsychotics to cause weight gain
and metabolic disturbances including an increase in the incidence of type 2 diabetes and high
cholesterol.

Other common side effects include:

 difficulty concentrating or speaking

 changes in blood pressure
 constipation
 difficulty sleeping
 drooling
 drowsiness
 mask-like face
 restlessness or need to keep moving
 sexual dysfunction
 shuffling walk
 tremor
 vision problems (blurred or double vision).

All antipsychotics can cause drowsiness. Most antipsychotics are associated with high rates of
discontinuation either because of side effects or a lack of effect.

4.2. Specific side effect of typical antipsychotic

 Extra pyramidal side effects such as, akathisia (Restlessness, fidgeting, pacing, rocking,
irritability), dystonia (Torsions and spasms of muscle groups), pseudo parkinsonism (Stiffness,
shuffling, mask-like face, tremor, rigidity), rabbit syndrome (Trembling of lower lip), pisa
syndrome leaning to one side (geriatric patients at higher risk), tardive dyskinesia (Facial signs
of TD: smacking, licking of lips, chewing movements, rolling or protrusion of tongue, Spastic
facial distortions, ‘tics’) are common. Further limited efficacy against negative and affective
symptoms as well as cognitive deficits.

Negative symptoms

Affective symptom

Cognitive deficit

Negative symptoms: Diminution of normal mental activity. Blunted (or flat) effects, catatonic
behavior alogia i.e. reduced speech, avolition i.e. lacking motivation.

Affective symptoms: Mood disorder with psychotic features.

Cognitive deficits: Executive function, attention and memory.

General adverse effects

 Neuromotor effects (e.g., extrapyramidal symptoms including dystonia, akinesia,

akathisia)*
 Metabolic effects (e.g., metabolic syndrome, change in body composition [weight, BMI],
fasting glucose, insulin sensitivity/resistance, dyslipidemia [total cholesterol, HDL
cholesterol, LDL cholesterol, triglycerides], blood pressure)*
 Prolactin-related effects and sexual dysfunction (e.g., hyperprolactinemia, AEs related to
prolactin elevations [e.g., galactorrhea/bloody galactorrhea, hypogonadism], erectile
dysfunction, infertility, oligo/amenorrhea, precocious puberty)*
 Agitation
 Constipation
 Somnolence* and fatigue
  Elevated transaminases
 Exercise intolerance
 Discontinuation syndrome (including symptoms related to motor [e.g., withdrawal-
induced dyskinesias, dystonias], autonomic (e.g., disturbed temperature regulation
nausea] and psychoses [e.g., rebound psychosis].

5. Antipsychotic Vs Psychotherapy

Definition

“Antipsychotic is a biomedical approach that has the goal of changing the function of the
nervous system to ease or eliminate the symptoms of various disorders.”

“Psychotherapy focuses on the cognitive, behavioral, and emotional lives of people

suffering from mental illness.”

5.1. Effectiveness of Psychotherapy

PSYCHOTHERAPY IS AN EFFECTIVE TREATMENT FOR NEGATIVE MENTAL

ISSUES THAT HAVE BUILT UP OVER MANY YEARS.

One major advantage to psychotherapy is that patients will be able to understand their
feelings of anxiety and learn how to turn negative feelings into a positive and productive
outlook. This talking type treatment can be conducted on a one on one basis or in a group
setting.

Usually, sessions are 50 minutes long and occur once a week. Psychotherapy treatment is
not only talking, other types of communication to get to the root of an emotional issue
can include expression through music, painting, writing and/or acting. The fact that
psychotherapy is a treatment that causes very little side effects due to lack of chemically
changing medications used, makes this method of treatment very attractive to many
people. Besides reducing psychological issues that can plague a person’s life and limit
their potential, some other advantages and positive benefits of Psychotherapy include:
 1. Developing better relationship skills.

2. Understanding and achieving personal goals.

3. Overcome illnesses such as depression, compulsive behaviours and eating disorders.

4. Boosts self-confidence.

5. Overall mood is improved.

6. Replaces negative thinking with positive thinking.

7. Learn relaxation techniques to effectively deal with daily stresses.

5.2. Effectiveness of antipsychotics

Antipsychotic drugs are the cornerstone in the management of psychotic disorders, but
most patients fail to have a “good” response in short-term trials. Therefore, alternative strategies
including dose escalation, switching to another antipsychotic, or co-treatment with polypharmacy
are often necessary. At any given time, more than 20% of the patients receive antipsychotic
polypharmacy in an attempt to manage suboptimal response to monotherapy. Because of the
limited evidence supporting the efficacy of this practice, far from being approved, decreasing it
is considered a key performance improvement and quality of care target in various states.
Nevertheless, to this day this practice is still prevalent in clinical care.

Surveys reveal that most of the patients treated with antipsychotic polypharmacy were in
fact inherited from other prescribers, yet most clinicians are reluctant to convert these patients to
antipsychotic monotherapy. Although switching from polypharmacy to monotherapy is generally
safe, data suggest a greater likelihood of dissatisfaction by patients or prescribers with the switch
to monotherapy.

Some major benefits of antipsychotics that are:

  Consistent drug delivery
 Predictable bioavailability
 Eliminates risk of patient deliberately or in advertently overdosing
 Avoidance of covert non-adherence to antipsychotic drug.
 Immediate identification of patients who decline their injection or fail to receive it
through forgetfulness.
 Instils hope of recovery.
 Reduction in intensity of hallucinations, delusions, thought disorder.
 Improvement in sleep, appetite and concentration.
 Minimization of distress (for suffer and families).
 Harm reduction- self harm, suicide, homicide.
 Reduction in rates of hospital admission.
 Reduction in number MHA assessments and detention rates.
 Asylum closure.

5.3. Psychotherapy works better in combination with antipsychotics among patients with
schizophrenia
 Antipsychotic drugs are limited in their ability to improve the overall outcome of
schizophrenia. Adding psychosocial treatment may produce greater improvement in functional
outcome than does medication treatment alone.

To evaluate the effectiveness of antipsychotic medication alone versus combined with

psychosocial intervention on outcomes of early stage schizophrenia.

Randomized controlled trial of a clinical sample of 1268 patients with early stage
schizophrenia, conducted at 10 clinical sites in China from 2005–2007.

Patients were randomly assigned to antipsychotic medication treatment only or

antipsychotic medication plus 12 months of psychosocial intervention, consisting of psycho-
education, family intervention, skills training and cognitive-behavioral therapy, administered
over 48 group sessions.

The rate of treatment discontinuation or change due to any cause, relapse or remission,
and assessments of insight, treatment adherence, quality of life and social functioning.

The rates of treatment discontinuation or change due to any cause were 32.8% in the combined
treatment group and 46.8% in the medication alone group. Comparisons with medication
treatment alone showed lower risk for any cause discontinuation with combined treatment
(hazard ratios [HR], 0.62; 95% confidence interval [CI], 0.52–0.74; p<0.001); and lower risk for
relapse with combined treatment (HR, 0.57; 95%CI, 0.44–0.74; p<0.001). The combined
treatment group exhibited greater improvement in insight (p<0.001), social functioning
(p=0.002), activities of daily living (p<0.001), and in 4 domains of quality of life as measured by
Medical Outcome Study Short-Form 36-item questionnaire (all p-values<0.02). Furthermore, a
significantly higher proportion of patients receiving combined treatment obtained employment or
accessed education (p=0.001).

Compared to those receiving medications only, early stage schizophrenia patients

receiving medications and psychosocial intervention had a lower rate of treatment
discontinuation or change, lower risk of relapse, and improved insight, quality of life and social
functioning.
 Bighelli and colleagues compared RCTs from their own earlier systematic reviews of
pharmacological (Leucht et al, 2017) and psychological (Bighelli et al, 2019) interventions for
schizophrenia. These comprehensive, up-to-date reviews both focussed on positive symptom
reduction as the primary outcome.

The current analysis therefore compared 80 trials of antipsychotics (18,271 participants) with
53 trials (4,068 participants) assessing various psychotherapies (CBT, metacognitive training,
mindfulness, acceptance and commitment therapy, experience-focused, counselling,
hallucination-focused integrative treatment, and AVATAR therapy). The main findings were:

 Patients enrolled into antipsychotic drug trials were more severely-ill at baseline as rated
on the Positive and Negative Syndrome Scale (PANSS: 93.97 vs 71.72), had a longer
history of illness (14 vs 12.37 years), and were older (38.95 vs 37.42 years) than those
enrolled into psychotherapy studies

 More than three-quarters (86%) of drug trials recruited only inpatients, whereas only one-
quarter (25.64%) of psychotherapy studies did so

 Drug trials had much larger samples than psychotherapy trials (313.53 vs 76.35 patients),
used many more study centres (36.69 vs 3.33) and often across multiple countries. Indeed,
psychotherapy trials were conducted mainly in only one country, with around half solely in
the UK

 Psychotherapy trials had an average duration that was 3 times longer than drug trials (19
vs 6 weeks)

 Control conditions differed markedly. While all antipsychotic trials used pill placebo,
psychotherapy employed various control groups e.g. other psychological interventions not
focused on the treatment of positive symptoms (20.8% of studies), inactive controls
(interventions intended to control for nonspecific aspects of the therapy: 17%), treatment
as usual (54.7%) and wait-list (13.2%)
 Little evidence is available for head-to-head comparisons of psychosocial interventions and
pharmacological interventions in psychosis. We aimed to establish whether a randomised
controlled trial of cognitive behavioural therapy (CBT) versus antipsychotic drugs versus a
combination of both would be feasible in people with psychosis.

We did a single-site, single-blind pilot randomised controlled trial in people with psychosis
who used services in National Health Service trusts across Greater Manchester, UK. Eligible
participants were aged 16 years or older; met ICD-10 criteria for schizophrenia, schizoaffective
disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis
service; were in contact with mental health services, under the care of a consultant psychiatrist;
scored at least 4 on delusions or hallucinations items, or at least 5 on suspiciousness, persecution,
or grandiosity items on the Positive and Negative Syndrome Scale (PANSS); had capacity to
consent; and were help-seeking. Participants were assigned (1:1:1) to antipsychotics, CBT, or
antipsychotics plus CBT. Randomisation was done via a secure web-based randomisation system
(Sealed Envelope), with randomised permuted blocks of 4 and 6, stratified by gender and first
episode status. CBT incorporated up to 26 sessions over 6 months plus up to four booster
sessions. Choice and dose of antipsychotic were at the discretion of the treating consultant.
Participants were followed up for 1 year. The primary outcome was feasibility (ie, data about
recruitment, retention, and acceptability), and the primary efficacy outcome was the PANSS total
score (assessed at baseline, 6, 12, 24, and 52 weeks). Non-neurological side-effects were
assessed systemically with the Antipsychotic Non-neurological Side Effects Rating Scale.
Primary analyses were done by intention to treat; safety analyses were done on an as-treated
basis. The study was prospectively registered with ISRCTN, number ISRCTN06022197.

Out of 138 patients referred to the study, 75 were recruited and randomly assigned—26 to
CBT, 24 to antipsychotics, and 25 to antipsychotics plus CBT. Attrition was low, and retention
high, with only four withdrawals across all groups. 40 (78%) of 51 participants allocated to CBT
attended six or more sessions. Of the 49 participants randomised to antipsychotics, 11 (22%)
were not prescribed a regular antipsychotic. Median duration of total antipsychotic treatment was
44·5 weeks (IQR 26–51). PANSS total score was significantly reduced in the combined
intervention group compared with the CBT group (–5·65 [95% CI −10·37 to −0·93]; p=0·019).
PANSS total scores did not differ significantly between the combined group and the
 antipsychotics group (–4·52 [95% CI −9·30 to 0·26]; p=0·064) or between the antipsychotics
and CBT groups (–1·13 [95% CI −5·81 to 3·55]; p=0·637). Significantly fewer side-effects, as
measured with the Antipsychotic Non-neurological Side Effects Rating Scale, were noted in the
CBT group than in the antipsychotics (3·22 [95% CI 0·58 to 5·87]; p=0·017) or antipsychotics
plus CBT (3·99 [95% CI 1·36 to 6·64]; p=0·003) groups. Only one serious adverse event was
thought to be related to the trial (an overdose of three paracetamol tablets in the CBT group).

A head-to-head clinical trial of CBT versus antipsychotics versus the combination of the two
is feasible and safe in people with first-episode psychosis.

5.4. psychotherapy works better in combination with antipsychotics among patient with
psychosis

Medications, psychotherapy and their combination have been shown to help people with
emotional or behavioral problems. Different kinds of problems, however, will respond
differently to various treatments; therefore, choosing the right treatment can be complicated.
Your choice of treatment should be based on the best available scientific evidence, as well as
your own willingness to try these treatments and to stick with them. Whatever the choice, these
discussions should be reviewed with your physician, psychologist or mental health professional.
Here are some things to consider:
Best Evidence
 For depression, two kinds of psychotherapy called cognitive-behavioral therapy and
interpersonal psychotherapy, as well as antidepressant medications, have been shown to be
helpful. There is some evidence that combining psychotherapy and medications may be more
effective than either treatment alone. People who are suicidal may need to be treated in a
hospital.
 For anxiety disorders, cognitive-behavioral therapy, antidepressant medications and anti-
anxiety medications have all been shown to be helpful. Research generally shows that
psychotherapy is more effective than medications, and that adding medications does not
significantly improve outcomes from psychotherapy alone.
 For alcohol and drug use disorders, cognitive-behavioral therapy and environment-based
therapies, as well as 12-step support programs, have been shown to be helpful. People with
 severe substance use problems may also benefit from the addition of certain medications that
reduce cravings or intoxication effects.
 For eating disorders, medical management may be necessary to maintain physical safety.
Cognitive-behavioral therapy, interpersonal psychotherapy and antidepressant medications have
all been shown to be helpful, and some evidence suggests that combining psychotherapy and
medications may be more effective than either treatment alone.
 For schizophrenia or bipolar disorder, most people will require treatment with
antipsychotic or mood-stabilizing medications. Research suggests that adding cognitive-
behavioral or family psychotherapy to the treatment can improve functional outcomes.
 For problems with parenting, marriage or adjustment, psychotherapy is usually the first
recommendation. This treatment can help you build skills and respond more appropriately to
stressors.

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