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Table 15.3 Unwanted effects of antipsychotic drugs
Psychomotor performance
The effects on cognition and psychomotor performance are complex and depend on the subject and the task assessed. Phenothiazines, in
particular, tend to induce drowsiness and fatigue. The sedation is related to the anti-histaminergic action and the α1- adrenergic receptor
blockade.
Extrapyramidal effects
Parkinsonian symptoms are the most common: tremor, rigidity, bradykinesia.
Akathisia (continuous motor restlessness) can be misinterpreted as incomplete control of psychotic symptoms.
Acute dyskinesia and dystonia: tonic contractions of muscles in the face, tongue and neck, and also of the truncal muscles, which may lead to
abnormal postures.
Seizures
Many neuroleptics can lower the seizure threshold and should be used with caution in untreated epileptic patients.
Endocrine effects
The disrupted dopamine control over pituitary function leads to increased prolactin release and swelling of the breasts (gynaecomastia) and
lactation (galactorrhoea).
Cutaneous effects
Chronic exposure to neuroleptics may lead to pigmentation and also photosensitivity.
Hepatotoxicity
Chlopromazine, in particular, may induce obstructive jaundice.
15
SCHIZOPHRENIA AND NEURODEVELOPMENTAL DISORDERS
Haematological effects
Agranulocytosis occurs rarely with typical neuroleptics but its incidence is much higher with clozapine. It is the most serious haematological
abnormality induced by antipsychotics. It presents with fever, fatigue and prostration, and ulceration of the mouth, throat, nose, rectum or vagina.
The mortality rate can reach approximately 30%.
Cardiovascular effects
Neuroleptics can induce significant postural hypotension with tachycardia. This is largely due to α- adrenergic receptor blockade.
Metabolic effects
Weight gain induced by neuroleptics may be related to a stimulation of appetite and/or a reduction in basal metabolic rate. Excessive weight is
associated with additional health risks such as hypertension and diabetes mellitus.
Anticholinergic effects
These effects are due to blockade of muscarinic receptors. They include decreased salivary flow, blurred vision and impaired accommodation,
constipation and urinary hesitancy or retention.
Sexual dysfunction
Antipsychotics can significantly affect sexual function. They can lead to loss of sexual drive, erectile and ejaculatory dysfunction, priapism and
menstrual irregularities.
these unwanted effects can be very significant. For example, obesity may occur in about one- third of patients
who receive fluphenazine or flupenthixol. This prevalence is four times higher than that in the general population. The host of anticholinergic effects induced by
antipsychotic drugs (constipation, difficulty in urinating,
dry mouth and blurred vision) is of particular concern in
elderly patients. Furthermore, the postural hypotension
induced by neuroleptics, and also the interference with
temperature control (hypothermia or hyperthermia),
are particularly troublesome in the elderly. The choice
of neuroleptic is, even today, often determined by its
unwanted effects and their acceptability. For example,
the sedation induced by chlorpromazine may be very
useful in an agitated schizophrenic, whereas its antimuscarinic effects may make it quite unacceptable in an
elderly patient with micturition problems. Haloperidol is
less hypotensive than chlorpromazine but has significant
extrapyramidal motor effects.
Neuroleptic malignant syndrome is an idiosyncratic
response to antipsychotic medication and consists of
hyperthermia (sometimes with profuse sweating), tachycardia, muscular rigidity and fluctuating levels of consciousness. It is a rare but potentially lethal complication
329THE NERVOUS SYSTEM
15
of antipsychotic drugs. The mortality rate can reach 20%–
30%. Dantrolene and dopaminergic agonists such as bromocriptine, and cooling and rehydration, have been used
to treat this syndrome, which may last for several days.
No particular class of antipsychotic is more or less likely
to induce this syndrome. Patients may be at greater risk
at the beginning of treatment or after a dose increase.
Atypical neuroleptics such as clozapine may be used to
manage patients who have already had an episode of
neuroleptic malignant syndrome.
Some complications of treatment with antipsychotic
drugs emerge after a specific duration of exposure to
these drugs. One such example is tardive dyskinesia.
This includes orofacial, trunk and limb dyskinesias. The
orofacial movements include protrusion of the tongue,
lip- smacking, pursing and sucking movements, puffing
of the cheeks and chewing. The involuntary limb movements are purposeless and jerky. The condition is both
socially and physically disabling. Spontaneous fluctuations in the severity of movements may occur from day
to day or even within hours or minutes. Most often, tardive dyskinesia does not disappear upon reduction of
the dose or withdrawal of the drugs. However, the dyskinesia may slightly improve or stabilize over a number
of years. Newer drugs, the ‘atypical neuroleptics’ such
as clozapine, olanzapine, risperidone and quetiapine,
have fewer unwanted effects. In particular, the incidence
SCHIZOPHRENIA AND NEURODEVELOPMENTAL DISORDERS
of extrapyramidal effects is much lower than with the
‘typical’ neuroleptics and they have higher efficacy than
the old neuroleptics in treating negative symptoms.
Clozapine shows unique efficacy in treatment- resistant
patients. Unfortunately, it is associated with an increased
risk of leukopenia and agranulocytosis (1%–2%). Its use
requires regular blood cell counts. A common characteristic of second generation, atypical antipsychotics such
as risperidone, is their high affinity for 5- HT2 receptors.
Therefore the new antipsychotics are better described
as dopamine and 5- HT receptor antagonists. The lower
potential for induction of extrapyramidal symptoms
could be due to complex interactions between 5- HT
and dopaminergic systems in the brain, and also to a
reduced degree of occupancy of dopaminergic receptors. In the case history it is not unlikely that Jane was
initially prescribed an old type of antipsychotic drug, so
the choice of a better, atypical compound may improve
her compliance.
Some antipsychotic drugs (e.g. haloperidol and flupenthixol) can be given as a depot slow- release preparation,
which is useful when compliance with treatment is unpredictable. This approach makes chronic schizophrenia
more manageable in the community, provided that adequate structures and support are available. The drugs are
administered as fatty acid esters (e.g. haloperidol decanoate, fluphenazine decanoate and pipotiazine palmitate)
by deep intramuscular injection at intervals of 1–4 weeks.
It is less easy to control the dose administered, especially
when a reduction of the dose is required. It may take several weeks to decrease plasma concentration or to control
the severity of unwanted effects.
sented by drugs with more complex profiles such as
aripiprazole (a partial agonist at D2 receptors), brexpiprazole (an agonist at D2 receptors and a partial agonist at
the 5- HT1A receptor) and cariprazine (a partial agonist at
D3/D2 receptors).
may benefit from cognitive therapy and occupational
therapy. Cognitive improvement, through social skill
development and cognitive behavioural treatments, hold
much promise but more research is required to maximize
the potential of these approaches, which are complementary to medical treatment. It is also important to note
that families and carers of schizophrenic patients require
long- term support because of the distressing and unpredictable nature of this chronic disease.
Comments on the management of
schizophrenia and the long- term prognosis
Schizophrenia is a complex mental illness that still
poses a therapeutic challenge in a significant number
of patients. It must be remembered that schizophrenia
is not a homogeneous disease, and recent research has
reinforced this concept of extreme heterogeneity. There
are numerous phenotypes and each poses its own problems during long- term management. In many patients
schizophrenia presents a chronic course, which is particularly disabling, especially because of the social isolation associated with negative symptoms. The evolution
of schizophrenia is sometimes complicated by the use of
addictive substances. Jane’s use (and abuse?) of alcohol
illustrates this tendency. The prognosis for each patient
depends on the balance between positive and negative
symptoms, the cognitive impairment, their response to
treatment, and also the lack of complicating factors such
as the development of drug addiction or other circumstances involving high levels of stress. In some patients
the response to treatment (especially the positive symptoms) is good and they may return to an almost normal level of functioning – at least between episodes of
relapse. The risk of suicide will not disappear during
the course of the disease and may be exacerbated by
the presence of depression. Of patients with schizophrenia, 10%–15% commit suicide. The long- term outcome
in schizophrenia is variable. Schizophrenia consists in
many cases of a sequence of exacerbations followed by
improvements, throughout lifetime. About one- third of
patients have one or a limited number of acute episodes,
with full or partial remission between episodes. Another
one- third of patients develop a chronic condition that
is stable and controlled to a variable extent by antipsychotic medication. Patients who relapse after cessation
of treatment require constant, long- term medication on
a type and dose of antipsychotic drug that they tolerate
reasonably well (in terms of unwanted effects). The value
of maintenance antipsychotic drug treatment in schizophrenia is supported by numerous studies. Research
A third generation of antipsychotic drugs is repre-
Apart from medical treatment, schizophrenic patients
330 SYSTEMS OF THE BODY
15
suggests that these drugs may have effects that are far
more complex than the blockade of neurotransmitter
receptors. Their chronic use may alter the expression of
genes critically involved in the generation and maintenance of synapses. Therefore, if a deficit in synapse
stabilization that is partly developmental is at the core
of the pathophysiology of schizophrenia, some antipsychotic drugs may affect, at least partly, the primary
cause of the disease. Future studies will be required to
consolidate these observations. Finally, the remaining
one- third of patients has a progressive debilitating psychosis with increasing impairment and no return to baseline. It is important to bear in mind that this core group
of chronic schizophrenic patients have only very moderate improvement, even if treated with newer drugs, and
remain the most challenging patients of all.
Other psychoses and neurodevelopmental
disorders
Psychotic states can be induced by exposure to a variety
of psychoactive compounds, some of which have been
mentioned already. The differential diagnosis of schizophrenia must take into account psychoses that may
occur in the context of disorders such as temporal lobe
epilepsy, multiple sclerosis, alcoholism or delirium and
dementia in elderly people.
Neurodevelopmental disorders are a complex family
of disorders. Examples of such disorders are autism and
Asperger’s syndrome.
Autism, also known as autism- spectrum disorder
(ASD), was defined as a syndrome and introduced to
the medical world by the Austrian child psychiatrist
Leo Kanner in 1943. The term reflects withdrawal from
others and marked self- centredness. Kanner described
a distinctive syndrome in children, characterized by a
solitary nature and an inability to relate to people and
to situations. Other features included the performance
of repetitive activities, mutism or abnormal language.
The abnormalities of speech in autistic children include
echolalia (repeating, like a parrot, words or sentences
without any understanding) and avoidance or confusion of personal pronouns (e.g. ‘he’ for ‘she’, or ‘you’
for ‘we’). Autistic children can have variable degrees of
intellectual disability. It is a common, highly heritable
(estimates ranging from 40% to 90%) and heterogeneous
disorder. More than 100 genes and genomic regions
have been associated with autism, and genetic variations include point mutations and copy number variations. Environmental risk factors associated with autism
include preterm birth or neonatal hypoxia, gestational
diabetes mellitus, maternal obesity and paternal age >50
years. Most recently, altered zinc levels in developing
neurons have been linked to developmental abnormalities in synapse maturation. During synaptic neurotransmission zinc enters the target neuron to bind to the
Shank2 and Shank3 proteins, to accelerate the maturation
of ionotropic glutamate AMPA receptors. Zinc shapes the
properties of developing synapses via Shank proteins.
A lack of zinc during early development might contribute to autism through impaired synaptic maturation and
neuronal circuit formation. It has been suggested that
the fundamental failure in autism is the lack of development of a ‘theory of the mind’: autistic children have
no concept of what other people think or feel, and this
leads to a lack of empathy and no, or very little, attachment to other people. Humans, animals and objects seem
to be treated alike, more like ‘tools’ to satisfy the child’s
needs. Such children sometimes display unusual features
of memory or skill. The worldwide prevalence of autism
is approximately 1% and it is more common in males.
The typical patterns of autistic behaviour usually emerge
after up to 18–20 months of apparently normal development. The diagnosis is based on a developmental history provided by parents and the observation of how the
child interacts with parents and other individuals. The
aetiology of autism is unknown and there is evidence for
genetic factors. It is likely that autism is a disorder with
a major neurodevelopmental component: a disruption
in brain formation in utero emerges in childhood when
the brain is growing rapidly and its connectivity evolves
towards maturation. Although autism and schizophrenia
are clearly different disorders, there are strong resemblances in terms of the existence of motor, speech and
behavioural abnormalities. Neuropathological abnormalities have been described in the hippocampus, mamillary
nuclei, amygdala and anterior cingulate cortex. Imaging
studies have revealed smaller volumes of the putamen,
pallidum, nucleus accumbens and amygdala, increased
thickness in the frontal cortex and decreased thickness
in the temporal cortex. Cerebellar abnormalities (such
as loss of Purkinje cells) are a constant feature. The
degree of cerebellar grey matter reduction is correlated
with autism symptom severity. There is evidence of disruption in white mater integrity and also whole- brain
altered connectivity, with evidence of both hypo- and
hyperconnectivity in various cerebral circuits. Some
of these changes are reported before the emergence of
behavioural symptoms. Autism is also associated with
epilepsy. Various types of epilepsy (e.g. absences, generalized tonic–clonic seizures and complex partial seizures)
affect 35%–45% of autistic children and adults. No definitive neurochemical abnormality has yet been defined as
pathognomonic for autism, but there is converging evidence in support of dopaminergic dysfunction.
Various drug treatments have been tried in autism and
have mostly symptomatic value. For example, antipsychotic drugs such as risperidone and aripiprazole can be
used for irritability, agitation and aggression. Other medications can target frequent comorbidities, such as anxiety
or epilepsy. Dietary interventions (e.g. supplementation
with vitamin B6 or magnesium) have been attempted and
can provide some improvement. More recently, there has
been interest in the therapeutic exploration of the neurohormonal oxytocin and vasopressin systems, which can
act as modulators of social behaviour. Therapy mostly
focuses on behavioural interventions, delivered by parents
SCHIZOPHRENIA AND NEURODEVELOPMENTAL DISORDERS
331THE NERVOUS SYSTEM
15
or therapists, and the development of structured education programmes. The various therapies are focused on
the aim of promoting independence in adulthood and
improved social functioning. Only a very small proportion of children with autism develop into normal adults.
The majority of autistic children will show psychiatric
impairments throughout life. In other cases there is some
improvement and it is possible for the patient to lead an
almost independent adult life.
Asperger’s syndrome has broadly similar features to
autism but is milder and does not become apparent until
after 3 years of age. DSM- 5 has included this disorder in
the ASD category but this classification remains controversial. It is much more common in boys than girls. Language
is affected (e.g. atypical syntax, idiosyncratic vocabulary)
and features stereotyped repetition of phrases. Unlike
with autism, intelligence may be normal or above average.
Patients affected by the syndrome may display exceptional
abilities in very narrowly defined fields. However, they
fail to develop peer relationships, show little reciprocity
and have very poor social communication skills. Overall,
social skills are very limited. Outcome is variable between
patients. A proportion of patients with Asperger’s syndrome may develop mild schizophrenia. They may display
obsessive behaviour and forms of bizarre violence.
There is still much debate about whether autism and
Asperger’s syndrome should be viewed as part of a con-
SCHIZOPHRENIA AND NEURODEVELOPMENTAL DISORDERS
tinuum or as two distinct conditions. Irrespective of the
best classification, it is likely that these represent two
related conditions characterized by major disruption of
social contact and abnormalities of affect.
Self-assessment case study
Richard was a rather quiet baby who gave no particular concern to his parents in his first 16 months of life.
They had noticed that Richard’s peers at the nursery
were much livelier than their son and seemed to take
more pleasure in interacting with adults, but they
assumed that their child was just shy and that he
would develop later. However, he gradually showed
clear lack of progress in the acquisition of even rudimentary language. He also developed a strong aversion to strangers and a tendency to violent temper
tantrums if his daily routines were upset. Otherwise,
he was a healthy, nice-looking child and physically
rather energetic.
with autism. His parents have already consulted several
specialists before they come to see you. They ask you to
give them your opinion and prognosis and indicate the
best treatment available.
answer the following questions:
1) Is the evolution of the condition described in this
normal development, so this is a typical presentation.
2) What is the neurobiological substrate of this disease?
abnormalities have been described in a variety of structures including the amygdala, cerebellum and cerebral
cortex. There is evidence of widespread alterations in
cerebral connectivity.
3) What are the treatment choices available?
Symptomatic treatment may be focused on alleviating comorbidities such as anxiety or seizures. Therapy
focuses mostly on behavioural approaches and structured education programmes aimed at improving the
socialisation of the autistic individual.
When Richard was 3 years old, he was diagnosed
After studying this chapter you should be able to
child compatible with a diagnosis of autism?
Yes, autism can emerge after 1–2 years of apparently
The cause of autism remains unknown. Structural
There is no optimum pharmacological management.
332 SYSTEMS OF THE BODY
DEPRESSION AND
ANXIETY
Chapter summary
1. Depressive disorders are common mental disorders that are
characterized by depressed mood, loss of interest or pleasure,
feelings of guilt or low self- worth, disturbed sleep and appetite, low
energy and poor concentration. Bipolar disorders are characterized
by altered episodes of mania and depressed mood. These disorders
can become lifelong disabling conditions and are associated with an
increased risk of suicide.
2. As a function of their severity, depressive disorders can be managed
with various pharmacological and non-pharmacological treatments,
such as psychotherapy, which could also be combined. Treatment
can lead to remission, but relapses may occur. Some patients
may have treatment resistance, which could be managed with
electroconvulsive therapy.
3. Antidepressant drugs belong to a variety of pharmacological
classes, and most of them modulate serotonergic and noradrenergic
(monoaminergic) transmission, which may become dysfunctional in
depression. There is a time lag between initiation of treatment and
onset of clinical efficacy, and treatment may need to be maintained
after apparent remission.
16
4. Anxiety disorders are the most common mental health disorders
and include phobic and non-phobic disorders. Relapses may occur
after remission. Non-pharmacological treatments include a variety
of psychotherapy approaches, such as cognitive behavioural therapy
and interpersonal therapy, and are recommended as the first line
of treatment. Pharmacological management includes selective
serotonin reuptake inhibitors and serotonin and noradrenaline
reuptake inhibitors. Anxiolytic drugs such as benzodiazepines, which
modulate GABA transmission, could also be prescribed, but for a
limited time, because of the higher risk of dependence.
16
5. Sleep is a vital physiological process that occurs in cycles and is controlled
by several neurotransmitter systems, including monoamines and
peptides. Insomnia is a disruption of normal sleep patterns, which can
be associated with environmental factors, stress and various medical
conditions. Sleep problems are common in anxiety disorders, and it is
well established that lack of sleep can worsen anxiety and increase the
risk of developing an anxiety disorder. Hypnotics such as the ‘z- drugs’,
which are short- acting non-benzodiazepine compounds, can be used in
DEPRESSION AND ANXIETY
insomnia management.
Introduction
Depression and anxiety represent, in a broad sense, transient states experienced by almost all individuals at some
point in their life. In contrast, neurological dysfunction caused by acute trauma or neuronal degeneration is
reflected in specific impairment, where no confusion exists
between the diseased state and the normal state. In some
individuals, depression and anxiety reach an intensity
and duration that totally disrupt normal life activities. The
classification of these disorders and their diagnostic criteria are regularly reviewed. The efficacy of most drugs used
for these conditions is moderate. It may still be believed,
erroneously by some, that depression and anxiety are not
major medical problems but rather transient states that
resolve, sooner or later, with full remission. However, as
the case history in Box 16.1 indicates, this is not so, and the
disease burden they represent for the patient, the family
and society is significantly underestimated.
Classification of mood disorders
‘If sorrow persists, then it is melancholia.’
Hippocrates (460–370 bc)
Descriptions of depressed states date back to Sumerian
and Egyptian documents. Later, Hippocrates, Galen and
other medical authors of antiquity continued to describe
depression and its possible causes and treatments. The
term ‘melancholia’ was used until the late 19th century,
when Kraepelin introduced the term ‘manic depression’,
to differentiate this severely disturbed mental state from
schizophrenia.
Depression is a general term that defines a family of
diseases. Table 16.1 gives the present classification of
these disorders according to the American Psychiatric
Association Diagnostic and Statistical Manual of Mental
Disorders 5 (DSM- 5). Most of this chapter is dedicated to
the discussion of major depression disorder and bipolar
disorder. The classification of depressive states is complex
and evolving, because the classification relies on clinical
phenotypes and not stringent aetiologically linked criteria.
Furthermore, currently, there are no clear biological markers or objective diagnostic tests that would allow for a reliable biology- based classification.
Clinical features of mood disorders
Depression is characterized by a series of changes that
gradually cause significant impairment of the activity of
the individual concerned. Table 16.2 shows typical core
symptoms of depression. These are psychological and
somatic.
Psychological symptoms include feelings of misery, guilt, hopelessness and general pessimism. Some
patients may become irritable or aggressive. Enjoyment
of various activities is lost (i.e. there is anhedonia, which
means ‘loss of pleasure’), and energy is low. Interest,
concentration and the ability to function efficiently and
make decisions are significantly impaired. Some patients
show very severe mental and physical slow- down
(retarded depression). Other patients present with a paradoxical reaction characterized by increased activity and
restlessness (agitated depression). Delusions and hallucinations may develop in some patients (depression with
psychotic features). These have the same negative and
destructive tone as the other symptoms.
Somatic symptoms are very common and often dominate the presentation of the case when patients consult
a doctor. Sleep is almost always disturbed, with earlymorning waking or difficulty in falling asleep. Most
patients lose weight, but in some patients, the opposite
is seen: they eat more and gain weight. Patients may also
suffer from nausea, constipation and headaches. Often,
patients find it easier to talk about the somatic symptoms
and feel rather embarrassed about revealing their psychological problems.
Depression can be rated using a variety of scales.
Examples of such include the Hamilton Depression
Scale, the Beck Depression Inventory and the Zung
Self- Rating Depression Scale. For example, in the Hamilton
334
SYSTEMS OF THE BODY
Box
16.1
William is a scientist who shares his time between work at
the university and writing about science. Over several weeks,
around his 45th birthday, he feels increasing fatigue and has
trouble sleeping. He has started going to bed early because
he feels tired all the time and because he tends to be awake
at dawn, unable to go to sleep again. His wife notices that
he no longer enjoys his hobbies. He is often irritable and
impatient with his children. Things take a turn for the worse
when William cancels a series of lectures and meetings
because he feels that he can no longer cope with his work.
His insomnia is getting worse, and he is losing weight. He
consults his doctor, who diagnoses depression and prescribes
venlafaxine. William is sceptical about treatment and is
reluctant to take the medication. He explains to his doctor
that he knows that antidepressant drugs can make you feel
unwell. He remembers from his childhood that his mother
had been suffering from periods of depression and had to
take drugs. She had never fully recovered, up to her accidental death a few years ago. William asks his doctor whether
other approaches could be used instead of drugs. He is worried about ‘getting addicted’ to drugs and not being able to
have a normal life without them. William’s doctor explains
that cognitive behavioural therapy is another option, and
that it may be possible to consider using this therapy.
sees no major change in the first 2 weeks, after 3 months of
treatment, he feels well and fully resumes his activities. His
mood is much improved, and while on a holiday, he decides
to stop taking the medication. Unfortunately, less than 2
years after this first episode, William feels unwell again, and
he needs to stop work and start a new course of venlafaxine. The drug is less efficacious this time, and the doctor is
very concerned about the feelings of guilt that William now
experiences and his heightened level of anxiety. He arranges
with William to start regular psychotherapy sessions with a
therapist, in parallel with the medication.
1. What triggers the depressive symptoms?
2. What is the cause of depression?
3. How can drugs help, and what other
4. Why do patients relapse?
5. What is the long- term management of depression?
Case history
William starts taking the medication and, although he
This case gives rise to the following questions:
non-pharmacological alternatives are there?
Depression Scale, 21 questions cover the various symptoms
and their intensity. The total score reflects the severity of
depression (Box 16.2). Depression is diagnosed according
to the DSM- 5 classification by the presence of at least five
out of nine key symptoms, present for at least 2 weeks and
of sufficient severity to cause significant distress or impairment in social, occupational or other areas of functioning.
Bipolar disorders (commonly called manic- depression
syndromes) are classified separately in DSM- 5, and they
16
DEPRESSION AND ANXIETY
Table 16.1 DSM- 5 classification of depressive disorders
Disruptive mood dysregulation disorder
Major depressive disorder
Persistent depressive disorder (dysthymia)
Premenstrual dysphoric disorder
Substance/medication- induced depressive disorder
Depressive disorder due to another medical condition
Other specified depressive disorder
Unspecified depressive disorder
Table 16.2 Symptoms of depression
Psychomotor retardation or psychomotor agitation
Fatigue or loss of energy
Diminished ability to concentrate
Diminished interest in social activity
Depressed mood
Feelings of guilt and worthlessness
Suicidal ideation
Insomnia
Weight loss and decreased appetite
Lack of interest and anhedonia
include three entities: bipolar disorder I, bipolar disorder
II and cyclothymia. These conditions are characterised
by alternating episodes of depression and mania. The
frequency of the episodes and their severity may increase
as the disease evolves. The manic attack is characterized by symptoms that are the opposite of those seen in
depression. Patients are overactive, disinhibited, unfocused and extravagant. They can become completely
irresponsible and display unlimited confidence in themselves. They may engage in unrealistic business ventures,
reckless driving, incredible buying sprees and numerous
sexual liaisons. They appear to need little food or sleep.
Thought and speech are intense, with a dominating flight
of ideas. Thought content can be grandiose, and delusions and hallucinations with a paranoid content may
develop. In extreme cases, hospital admission is required
(under the provisions of national mental health acts
such as the UK Mental Health Act 2007) because of the
patient’s loss of insight into their illness.
Epidemiology of depressive and bipolar
disorders and their natural evolution
According to the World Health Organisation, depressive
disorders are among the top 20 medical conditions associated with a significant burden of disease. Prevalence
and incidence are in similar ranges worldwide. Women
THE NERVOUS SYSTEM
335
16
Box
16.2
Patient’s name
________________________________________________________________________________________________________________________
Date of assessment
________________________________________________________________________________________________________________________
To rate the severity of depression in patients who are already diagnosed as depressed, administer this questionnaire. The higher
the score, the more severe the depression.
DEPRESSION AND ANXIETY
For each item, write the correct number on the line next to the item (only one response per item).
____________ 0 = Absent
____________ 0 = Absent
The Hamilton Rating Scale for Depression (to be administered by a healthcare
professional)
1. DEPRESSED MOOD (Sadness, hopeless, helpless, worthless)
1 = These feeling states are indicated only on questioning
2 = These feeling states are spontaneously reported verbally
3 = Communicates feeling states non-verbally—i.e. through facial expression, posture, voice and tendency to
weep
4 = Patient reports these feeling states VIRTUALLY ONLY in his spontaneous verbal and non-verbal
communication
2. FEELINGS OF GUILT
1 = Self- reproach, feels he has let people down
2 = Ideas of guilt or rumination over past errors or sinful deeds
3 = Present illness is a punishment. Delusions of guilt
4 = Hears accusatory or denunciatory voices and/or experiences threatening visual hallucinations
3. SUICIDE
____________ 0 = Absent
1 = Feels life is not worth living
2 = Wishes he were dead or any thoughts of possible death to self
3 = Suicidal ideas or gesture
4 = Attempts at suicide (any serious attempt rates 4)
4. INSOMNIA EARLY
____________ 0 = No difficulty falling asleep
1 = Complains of occasional difficulty falling asleep—i.e. more than ½ hour
2 = Complains of nightly difficulty falling asleep
5. INSOMNIA MIDDLE
____________ 0 = No difficulty
1 = Patient complains of being restless and disturbed during the night
2 = Waking during the night—any getting out of bed rates 2 (except for purposes of voiding)
6. INSOMNIA LATE
____________ 0 = No difficulty
1 = Waking in early hours of the morning but goes back to sleep
2 = Unable to fall asleep again if he gets out of bed
7. WORK AND ACTIVITIES
____________ 0 = No difficulty
1 = Thoughts and feelings of incapacity, fatigue or weakness related to activities, work or hobbies
2 = Loss of interest in activity, hobbies or work—either directly reported by patient, or indirect in listlessness,
indecision and vacillation (feels he has to push self to work or activities)
3 = Decrease in actual time spent in activities or decrease in productivity
4 = Stopped working because of present illness
336 SYSTEMS OF THE BODY
Box
16.2
The Hamilton Rating Scale for Depression (to be administered by a healthcare
professional)—cont’d
8. RETARDATION (PSYCHOMOTOR) (Slowness of thought and speech; impaired ability to concentrate; decreased
motor activity)
____________ 0 = Normal speech and thought
1 = Slight retardation at interview
2 = Obvious retardation at interview
3 = Interview difficult
4 = Complete stupor
9. AGITATION
____________ 0 = None
1 = Fidgetiness
2 = Playing with hands, hair, etc.
3 = Moving about, can’t sit still
4 = Hand wringing, nail biting, hair- pulling, biting of lips
10. ANXIETY (PSYCHOLOGICAL)
____________ 0 = No difficulty
1 = Subjective tension and irritability
2 = Worrying about minor matters
3 = Apprehensive attitude apparent in face or speech
4 = Fears expressed without questioning
16
DEPRESSION AND ANXIETY
11. ANXIETY (SOMATIC) Physiological concomitants of anxiety (i.e. effects of autonomic overactivity, ‘butterflies’,
indigestion, stomach cramps, belching, diarrhoea, palpitations, hyperventilation, paraesthesia, sweating,
flushing, tremor, headache, urinary frequency). Avoid asking about possible medication side effects (i.e. dry
mouth, constipation)
_____________ 0 = Absent
1 = Mild
2 = Moderate
3 = Severe
4 = Incapacitating
12. SOMATIC SYMPTOMS (GASTROINTESTINAL)
_____________ 0 = None
1 = Loss of appetite, but eating without encouragement from others. Food intake about normal
2 = Difficulty eating without urging from others. Marked reduction of appetite and food intake
13. SOMATIC SYMPTOMS GENERAL
_____________ 0 = None
1 = Heaviness in limbs, back or head. Backaches, headache, muscle aches. Loss of energy and fatigability
2 = Any clear- cut symptom rates 2
14. GENITAL SYMPTOMS (Symptoms such as loss of libido, impaired sexual performance, menstrual disturbances)
_____________ 0 = Absent
1 = Mild
2 = Severe
15. HYPOCHONDRIASIS
_____________ 0 = Not present
1 = Self- absorption (bodily)
2 = Preoccupation with health
3 = Frequent complaints, requests for help, etc.
4 = Hypochondriacal delusions
Continued
337THE NERVOUS SYSTEM
16
Box
16.2
The Hamilton Rating Scale for Depression (to be administered by a healthcare
professional)—cont’d
16. LOSS OF WEIGHT
_____________ A. When rating by history:
0 = No weight loss
1 = Probably weight loss associated with present illness
2 = Definite (according to patient) weight loss
3 = Not assessed
DEPRESSION AND ANXIETY
_____________ 0 = Acknowledges being depressed and ill
_____________ A. Note whether symptoms are worse in morning or evening. If NO diurnal variation, mark none
_____________ 0 = Absent
17. INSIGHT
1 = Acknowledges illness but attributes cause to bad food, climate, overwork, virus, need for rest, etc.
2 = Denies being ill at all
18. DIURNAL VARIATION
0 = No variation
1 = Worse in A.M.
2 = Worse in P.M.
B. When present, mark the severity of the variation. Mark ‘None’ if NO variation
0 = None
1 = Mild
2 = Severe
19. DEPERSONALIZATION AND DEREALIZATION (Such as feelings of unreality and nihilistic ideas)
1 = Mild
2 = Moderate
3 = Severe
4 = Incapacitating
20. PARANOID SYMPTOMS
_____________ 0 = None
1 = Suspicious
2 = Ideas of reference
3 = Delusions of reference and persecution
21. OBSESSIONAL AND COMPULSIVE SYMPTOMS
_____________ 0 = Absent
1 = Mild
2 = Severe
are almost twice as likely to be diagnosed with depression as men. For example, estimates of the prevalence
rates of a major depressive episode in 2017 in the USA
were 8.7% in females compared with 5.3% in males. A
cross- sectional survey of 11 countries, published in 2011,
found that the lifetime prevalence of bipolar spectrum
disorders was 2.4%.
Depression can occur at any age; it affects children, adolescents, adults and the elderly. For many patients, major
depression is a lifelong disorder that consists of episodes
of relapse separated by remission intervals. Bipolar disorders are also highly recurrent, and full recovery is rare.
The mean age of onset of depression has decreased gradually from the 40- to 50-year age range to the 25- to 35-year
Total Score______________
age range. Stress is considered one of the main risk factors
for the development of depression. Evidence suggests that
negative psychosocial factors (e.g. bereavement or loss of a
job or social status) may trigger the first depression episode.
However, this is more likely to happen in susceptible individuals (i.e. against a predisposing genetic background).
Depression is associated with an increased mortality
rate compared with the rest of the population, due to an
increased suicide rate. Accumulating evidence indicates
that major depressive disorder may confer a higher risk
for several non-communicable diseases such as diabetes,
obesity, coronary heart disease, stroke and dementia. The
converse is also true, in that these chronic health conditions
appear to increase the likelihood of developing depression.
338 SYSTEMS OF THE BODY