Depressive disorders

Depression is a common condition in the society. It is given many names in the society, such
as kufunganya or kufungisisa. It is a mood disorder characterised by the presence of a sad,
empty or irritable mood accompanied by somatic & cognitive changes that significantly
affect the individual’s ability to function. Depression is the most common mental illness in
the population, but it often goes undiagnosed. The core symptoms of depression are low
mood, anhedonia and anergia. In most cases patients recover from their depressive
episodes. However, in some cases, patients exhibit clinical symptoms and cessation of social
functions & responsibilities. Depression in the general population is attributed to many
things, a lot of which are not true.

Depression affects 10-20% of the population, and the lifetime risk of suffering from
depression is 15%. Depression affects females about twice as much as it affects men. The 6-
month prevalence is about 2%. The mean age of onset is the late 20s.

Risk factors
The risk factors for developing depression are:

 Family history. It is estimated that the risk of developing depression is 37% if you
have a 1st-degree relative who has suffered a depressive episode. In addition, these
families also have high rates of anxiety disorders & neuroticism, suggesting a shared
genetic basis.
 Adverse childhood experience. These include loss of a parent1, lack of parental care,
parental alcoholism/antisocial traits and childhood physical & sexual abuse. The risk
increases with cumulative adverse childhood experiences. High intelligence & one
good adult relationship are protective factors.
 Adverse life events. This is true particularly for loss events, such as a spouse dying.
The risk increases 2-3 months after the event. Other loss events include job dismissal
and a recently-ended relationship.
 Personality traits. These include anxiety, impulsivity and obsessionality. These have
high neuroticism scores.
 Comorbid physical illness. A chronic severe painful illness is a common finding. Other
neurological disorders such as Parkinson’s, multiple sclerosis, stroke and epilepsy are
common causative conditions. Higher rates are also noted in post-MI patients,
diabetic patients and cancer patients. 50% of patients will have another depressive
episode following the first one.

1
This, however, is inconsistent across studies.
  Marital status. Depression is higher amongst divorced & separated people than
amongst married people. This is significant in men, and in women the disparity exists
but is less clear-cut.
 Family size. Having 3 or more children below the age of 11, lacking paid employment
and lacking a confiding relationship are all associated with an increase in incidence of
depression.
 Socioeconomic status. Hunger (30% hungry people vs. 12% in normal population) &
low income (56% vs. 31%) are common causes.

There are no differences in the incidence of mood disorders that can be attributed to race.

Classification of depressive mood disorders

The main types of depressive mood disorders are:

 Disruptive mood dysregulation disorder. This is a fairly new classification. It

describes a presentation in children with persistent irritability and frequent episodes
of extreme lack of behavioural control2. The temper outbursts are typified by severe
recurrent verbal & behavioural outbursts that are grossly out of proportion in
intensity & duration of the provocative situation (criterion A). The outbursts occur 3
or more times a week (criterion C) and they are inconsistent with developmental
level (criterion B). The mood between episodes is persistently irritable or angry
(criterion D). Criteria A-D should be present for at least 12 months. It applies to
children up to the age of 12 years of age.
 Major depressive disorder. This is the classical condition in this group of disorders.
For a positive diagnosis of major depressive disorder to be made, the patient should
have had 5 or more depressive core symptoms for at least 2 weeks and with clear-
cut changes in cognition, affect and neurovegetative function and inter-episode
remissions (criterion A). The symptoms should cause clinically significant distress or
impairment in social, occupational and other important areas of function (criterion
B). The symptoms should not be secondary to alcohol or substance abuse (criterion
C) and a comorbid mental disorder (criterion D). Also, there should never have been
a manic or hypomanic episode, unless they are substance- or medication-induced
(criterion E). The symptoms (which are mainly neurovegetative) that are being
looked at are: depressed mood for most of the day; marked diminution of pleasure
& interests (anhedonia); significant weight gain/loss when not dieting or exercising;
insomnia/hypersomnia; low energy (anergia); feelings of worthlessness &
excessive/inappropriate guilt; diminished ability to think or concentrate; and
recurrent suicidal ideation. A diagnosis based on a single episode is possible.
 Persistent depressive disorder (also called dysthymia). This is a depressive disorder
that is more chronic. It is diagnosed when a depressive episode has persisted for

2
It was created to avoid over-diagnosis & treatment of bipolar affective disorder in children.
 more than 2 years in adults or 1 year in children (criterion A). The presence of any 2
of the following symptoms also helps establish the diagnosis: increased/decreased
appetite; insomnia/hypersomnia; low energy; low self-esteem; poor
concentration/difficulty making decisions; and feelings of hopelessness (criterion B).
During the 2 years, the patient must not have gone without the above symptoms for
more than 2 months at a time (criterion C).
 Premenstrual dysphoric disorder. This is a disorder in which in the majority of the
menstrual cycles, at least 5 symptoms must be present in the final week of the
menstrual cycle, start to improve after the onset of menses and become
minimal/absent one week after menses (criterion A). At least one of the following
symptoms are present: marked affective lability (mood swings, feeling suddenly
sad/tearful, increasing sensitivity to rejection); marked irritability/anger/increased
interpersonal conflicts; marked depressed mood, feelings of hopelessness and self-
depreciating thoughts; and marked anxiety & tension (criterion B). The 5th symptoms
can be any of: anhedonia; subjective difficulty in concentration; lethargy, easy
fatigability and/or marked lack of energy; marked change in apetite;
hypersomnia/insomnia; a sense of being overwhelmed/out of control; and physical
symptoms such as breast tenderness/swelling, joint/muscle pain, bloating and
weight gain (criterion C).

Other depressive disorders are:

 Psychotic depression. This is depression that has psychotic symptoms such as

hallucinations and delusions. The psychotic features may be mood-congruent, in
which the content of all delusions is consistent with the typical depressive themes:
personal inadequacy, guilt, disease, death, nihilism or deserved punishment. They
may also be mood-incongruent, in which the content of the delusions does not
involve typical depressive themes, or it has a mixture of mood-congruent & mood-
incongruent themes. Olfactory hallucinations are common, and often the patient can
smell rotting flesh. Patients also experience auditory hallucinations which are often
derogatory in nature. Suicide risk is high. Some may develop psychomotor
retardation, which may increase to the point where a patient simply sits motionless.
This is called depressive stupor. This is often fatal, and therefore calls for emergency
ECT (electroconvulsive therapy).
 Atypical depression. This is depression that is typified by clinical features that are
different from the usually other symptoms of depression. These symptoms include
mood reactivity (the capacity to be cheered up when presented with positive events:
criterion A), significant weight gain & increase in appetite, hypersomnia, leaden
paralysis (heavy leaden feeling in the arms & legs) and a long-standing pattern of
interpersonal rejection sensitivity that lead to significant social and/or occupational
impairment (criterion B: the rest of the symptoms).
  Mixed anxiety & depressive disorder. This is also called anxious distress and is
defined by the presence of any 2 signs/symptoms of anxiety together with those of
depression. The signs of anxiety are: feeling keyed up/tense; feeling unusually
restless; difficulty concentrating because of worry; fear that something awful is going
to happen; and fear that the individual might lose control of themselves. The
condition can be divided into mild (2 anxiety symptoms), moderate (3 anxiety
symptoms), moderate-severe (4-5 anxiety symptoms) and severe (4-5 anxiety
symptoms with motor agitation).
 Peri-partum depression. This is a condition that develops either during pregnancy or
during the first 4 weeks postpartum. It is important because it affects about 10% (3-
6%, DSM 5) of women after delivery. It has been shown that mood & anxiety
symptoms that develop during pregnancy increase the risk of postpartum major
depressive disorder. It can present with or without psychotic symptoms, and these
occur in 1 in 500-1000 pregnancies. The risk of peripartum psychosis is increased in
women with prior postpartum mood episodes, women with a history of
depressive/bipolar disorder and women with a family history of bipolar disorders.
Peri-partum depression has a significant impact as it reduces the interaction
between mother & child, which could lead to neglect of the foetus, delayed child
development and impaired psychosocial development of child. It is also associated
with infanticide, particularly in peri-partum depression with psychosis.

For 2 separate episodes to be considered different, they need to be separated by at least 2

months without significant symptoms of depression.

Neurobiology of depression
The brains of depressed individuals have both structural & functional changes.

 Structural changes. Depression is associated with ventricular enlargement & sulcal

prominence: brain atrophy. The degree of brain atrophy correlates to duration of the
current episode & illness and duration of untreated depression. There is volume loss
in the prefrontal cortex & medial prefrontal cortex. These neurons normally project
to the hippocampus, amygdala and hypothalamus. There is also loss of hippocampal
volume, and this also correlates to cognitive deficits of depression. This loss of
volume is particularly found in refractive cases. There is also an increase in white
matter lesions in older patients. Other brain structures that atrophy during
depression include the basal ganglia and thalamus. There is decreased anterior brain
metabolism that is more pronounced on the left side, and this is seen on PET
(positron emission tomography).
 Functional changes. Depression is a result of depleted levels of norepinephrine
(mood & energy), serotonin (sleep, appetite, memory and mood) and dopamine
(psychomotor activity). This is the basis of the monoamine hypothesis of depression.
 There is also reduced GABA function and abnormal synaptic density & neuronal
plasticity in the neurons in the hippocampus. There are also blunted GH & prolactin
responses to tryptophan and citalopram, blunted GH responses to clonidine &
apomorphine and increased GH response to physostigmine. There is increased
cortisol in about 50% of patients and there is a blunted TSH response to a TRH
challenge3.

Clinical features
Depression is diagnosed by the presence of all core symptoms plus additional symptoms.
The core symptoms of depression are:

 Low mood. This is present most of the day nearly every day and with little variation.
There is also a lack of responsiveness of the patient to changes in circumstances
(blunted affect). There may be diurnal variation of mood, with mood being lowest in
the morning and improving during the day.
 Anhedonia. This is marked diminution in interest & pleasure in most/all activities
most of the day nearly every day. This may be subjective based on patient or
objective based on observations by others.
 Anergia. This is low energy for most of the day, or generalised fatigue.

Other neurovegetative symptoms are:

 Weight change. This is a change in weight in a person who is neither exercising nor
dieting. It may be associated with a change in appetite.
 Disturbed sleep. This may be hypersomnia or insomnia. The insomnia is usually
terminal insomnia.
 Psychomotor agitation or retardation. This has to be based on other people’s
observations and not just subjective feelings of restlessness or being slowed down.
 Reduced libido.
 Feelings of worthlessness & excessive guilt. This guilt may be delusional or not.
 Reduced concentration. This also includes indecisiveness.
 Suicide ideation. These may or may not have been acted upon.

Patients may also have psychotic symptoms. These are more common in psychotic
depression:

 Delusions. These include delusions of poverty, personal inadequacy, guilt over

presumed misdeeds, responsibility for world events, deserving punishment and
other nihilistic delusions.
 Hallucinations. They can be auditory, visual or olfactory. Auditory hallucinations can
be defamatory, accusatory, cries for help or screaming. Olfactory hallucinations can
3
This is associated with increased risk of relapse even during antidepressant therapy, and the blunted
response does not normalise with treatment.
 be bad smells, such as rotting food, faeces and decomposing flesh. Visual
hallucinations can be of tormentors, demons, the devil, dead people and scenes of
death & torture. These are examples of mood-congruent symptoms, although mood
incongruent symptoms4 may be present as well.
 Catatonic symptoms. The patient may have marked psychomotor retardation
(depressive stupor) instead.

Depression is classified into mild, moderate and severe based on the number of symptoms
& the patient’s functionality:

Mild 2 typical symptoms + 2 other core symptoms and minor social & occupational
impairment.
Moderate 2 typical symptoms + 3-4 other core symptoms and considerable social &
occupational impairment.
Severe 3 typical symptoms + 4 or more other symptoms and unable to function
normally

People with depression often present with other comorbid illnesses. Men more frequently
present with substance use disorders (e.g. alcohol use) while women present with comorbid
anxiety or eating disorders. These conditions worsen the prognosis of the illness.

History taking & examination of depressed patient

A depressed patient is highly unlikely to talk a lot. Therefore listen carefully, do not rush the
patient and show that you understand the patient & what they are going through. Also
consider that people in the community may not take her condition seriously, so you need to
show compassion.

In the history, key areas to look for are:

 Any clear psychosocial precipitants.

 Use of drugs or alcohol. If the patient drinks, you need to a CAGE score or an AUDIT.
 Past history of previous mood symptoms. This includes periods of low/elevated
mood and previous suicide attempts.
 Previous effective treatment.
 Premorbid personality.
 Family history of mood disorder.
 Physical illness.
 Current medication.
 Ask about whether the patient has any babies, if the patient is female.

On the mental state examination, you need to focus on

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Mood-incongruent symptoms may point towards schizoaffective disorder or schizophrenia.
  Mood & somatic symptoms.
 Psychotic symptoms.
 Anxiety symptoms.
 Suicide ideations. You must ALWAYS DO A SUICIDE RISK ASSESSMENT.
 Objective assessment of psychomotor retardation/agitation.

In the history, you need to rule out the presence of any manic episodes that the patient may
have developed.

Diagnosis & investigation

Diagnosis of depression is primarily based on a good psychiatric history, since biopsying the
brain is not feasible for every case of depression. Ask about the typical symptoms (low
mood, anergia & anhedonia) as well as other core symptoms. You may use a standardised
rating scale such as the Hamilton Depression Rating Scale (HAM-D). This scale scores each
symptom and the scores added up to determine the severity of depression:

The scale has 21 areas of interest, but the score is calculated on the first 17.
Score Classification
0-7 Normal mood
8-13 Mild depression
14-18 Moderate depression
19-22 Severe depression
>23 Very severe depression

There is no particular investigation that diagnoses depression; investigations focus on

excluding possible treatable causes. The investigations done in depression are:

 Standard tests: FBC (full blood count), LFT (liver function tests), U&Es (urea &
electrolytes), TFTs (thyroid function tests), glucose, calcium and HIV test.
 Focused investigations. These depend on indications from the history & examination.
They include thyroid antibodies, antinuclear antibodies, syphilis serology, arterial
blood gas, breath/blood alcohol, blood & urine toxicology, additional electrolytes
(CAMP & zinc) and imaging (CT, MRI & EEG).

Management of depression
Management of depression, as with every other condition, is divided into somatic therapy,
psychotherapy, social management and rehabilitation.

 Somatic therapy. Somatic therapy involves iatrogenic interventions, and it is divided

into pharmacotherapy and brain stimulation treatments.
o Pharmacotherapy. Pharmacotherapy is indicated in a patient who has: a past
history of moderate/severe depression; an initial presentation of sub-
threshold symptoms that have been present for a long period of time; and
sub-threshold symptoms that persist after other interventions.
Pharmacotherapy can be initiated on an outpatient basis, and only severe
cases required admission (or patients that have attempted/will attempt
suicide). Antidepressants are effective in 60-75% of patients. They work by
increasing neurotransmitter levels in the various systems of the brain (since
depression is associated with a decline in neurotransmitter levels). The
decision of which antidepressant to use will depend on patient factor (age,
sex, comorbid physical illness and previous response to antidepressants),
tolerability of drugs and symptomatology (sleep symptoms, lack of energy,
OCD symptoms and risk of suicide). The agents you can use are: TCAs
(tricyclic antidepressants), MAO inhibitors, SSRIs (selective serotonin
reuptake inhibitors), SNRIs (serotonin/norepinephrine reuptake inhibitors).
Antidepressants are generally safe and they are not addictive. For the 1st
episode, you can treat for 6-12 months; for the 2nd episode, you treat for 12-
24 months. For the 3rd episode, you treat the patient with antidepressants for
life. When switching between antidepressants, you need an adequate
washout period. Always watch out for development of manic symptoms.
If after 9-12 months patients report that they have minimal/no symptoms
and they have returned to normal daily function, then you can stop
medication. You can do a step-wise reduction in the dose, reducing the dose
gradually over at least 4 weeks as you run the risk of immediate relapse of
the patient. Discuss the plan with the patient before reducing the dose.
Describe the early symptoms of relapse and plan routine & emergency
follow-up.
o Brain stimulation treatments. The brain stimulating treatment present is
electroconvulsive therapy (ECT). In electroconvulsive therapy, there is an
electric current that is passed through the brain, inducing a short seizure. It is
highly effective for treatment of depression, particularly psychotic depression
associated with depressive stupor. It is given with a light general anaesthetic
& muscle relaxant, and it has EEG monitoring. The mode of action in ECT is
not well understood, but there are many theories:
1. ECT acts as a powerful anticonvulsant that reduces functional activity
in specific brain regions related to the therapeutic response
(anticonvulsant/altered functional activity theory).
2. ECT induces EEG changes similar to those seen during sleep, and these
correlate to clinical improvement (anti-delirium/restorative sleep
theory).
 3. ECT works by correcting a dysregulation of neuropeptides through
diencephalic stimulation (neuroendocrine theory). It enhances the
production & release of several neuropeptides.
4. ECT is also believed to work by inducing formation of new blood
vessels in the brain (neuro-angiogenesis theory).
ECT is only effective for a certain period of time. It is important that you
ensure that you have a plan of action for when the anti-depressive effects
wear off. There are side effects associated with ECT. These include loss of
memory (short-term as an early effect, long-term as a late side effect)
Somatic interventions are only indicated for patients with moderate & severe
depression.
 Psychotherapy. Psychotherapy is used for all levels of depression. There are different
forms of psychotherapy available for depressed patients:
o Psychoeducation. You need to explain the diagnosis to the patient and
reassure the patient that depression is a common & treatable illness. You
need to reassure them that they are not mad, and explain to them that it is
normal to have physical symptoms as a result of stress & depression. Help on
various things, such as sleep hygiene, regular gentle exercise, etc. should be
provided.
o Cognitive behavioural therapy. This is used to encourage the patient to
engage in pleasurable activities. Patients should also explore social support
networks and participate in them. The idea behind cognitive behavioural
therapy is to encourage new behaviours in the patient, and these should
change the patient’s mood and generate positive thoughts: a triangle

Mood

Behaviour Thoughts

The change in behaviour generated by CBT is a result of conclusions &

assertions that are reached by the patients themselves. Therefore, as the
clinician, your job is to counsel the patients in such a way that they realise
that their thoughts are the ones that have influence over how they feel.