What is the cause of depression?

06 February 2013

What is the cause of depression?

Exactly what causes depression is not known, but research has revealed several possible causes and contributory factors. These include both biological/physical and social/psychological factors.

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Between 80-90 percent of all depressed people respond to treatment and almost all sufferers who are appropriately treated will experience at least some symptom relief.

The first aim of treatment is to ensure the safety of the patient for whom hospitalisation may be required (i.e. suicidal/unable to care for self). Secondly, a complete diagnostic evaluation must be carried out. This includes a full personal and family history as well as a history of illnesses, medication and recreational drugs/alcohol used, activities, personality type and support system.

A physical examination may also be required to evaluate underlying physical illness, which may cause or worsen depression, e.g. thyroid illness. It is important to detect medical problems, as these require separate, appropriate treatment.

Thirdly, a treatment plan has to be formulated which takes into account both immediate symptoms and the patient’s future well-being. This would include medication, psychotherapy, life-style changes and the addressing of stressors. Stressful life events are associated with an increased relapse rate in mood disorder sufferers.

Psychotherapy

Psychotherapy is also known as “talking therapy” and involves verbal interaction between a trained mental health professional and a patient who may be experiencing emotional or behavioural problems. There are several different types of psychotherapy, which may differ in the techniques used based on the psychological principles emphasised, but the underlying aim is to enable the patient to gain insight into him or herself and thereby change maladaptive thoughts, feelings and behaviour.

Research has shown that some forms of psychotherapy are as effective as medication in treating mild to moderate depression. Medication tends to bring about results more rapidly, but the benefits of psychotherapy may be more enduring. It is generally agreed that the best form of treatment is a combination of both pharmacotherapy and psychotherapy.

Cognitive Behavioural Therapy (originally developed by Aaron Beck)

This is a short-term structured therapy using active collaboration between patient and therapist in order to reach the therapeutic goals. This treatment approach is based on the theory that one’s feelings and behaviour are controlled by how one thinks and perceives one's world.

Those who become depressed tend to see themselves negatively, believe that others see them in a similar light, expect to fail or experience continued difficulties, feel hopeless and have negative expectations of life and the future. The therapist uses various techniques to identify and demonstrate the negative thought processes, which are then challenged. Patient and therapist then work together on changing negative thought patterns and beliefs, so that a more realistic and positive mindset may develop. Overall therapy is relatively short, lasting up to 25 weeks.

Interpersonal psychotherapy (developed by Gerald Klerman)

The underlying hypothesis in this therapy is that disturbed social or personal relationships may cause or precipitate a depressive episode. The depression, in turn, impacts negatively on the relationships, which then further exacerbates the illness. Therapy deals with one or two current interpersonal problems and helps the patient understand how depression and interpersonal conflicts are related. The interpersonal therapy programme usually consists of 12 – 16 weekly sessions.

Psychodynamic psychotherapy (developed by Freud, Kohut, Jacobson and Abraham)

This therapy is based on the idea that current behaviour and life experience is influenced by earlier experiences, hereditary traits and present reality. It takes into account the effects that emotions and unconscious material can have on human behaviour. This is usually a long-term open-ended therapy which may continue for years and is often less interactive.

Family therapy

This is not usually a primary therapy for the treatment of a MDD, but helping to identify negative interactions within a family can help to reduce stress and thereby decrease relapse. Family therapy examines the role of the mood-disordered member in the overall psychological well-being of the whole family. It also examines the role of the entire family in maintaining the patient’s symptoms. Family therapy may also provide emotional support for the family of a sufferer.

Antidepressants

Pharmacotherapy for depressive disorders has advanced considerably over the past twenty years and there are now a large number of drugs to choose from. All antidepressants are equally effective, provided an adequate dosage is taken for a sufficiently long time. Different drugs may be prescribed for different individuals, depending on the symptoms presented. Some antidepressants are more energising, while others may cause weight loss or gain. A decision regarding which drug to use is often made on the basis of tolerability of potential side effects.

Antidepressants do not act rapidly. A certain dosage and concentration has to be reached before they become effective. This usually takes about a month, but may take six to eight weeks in the elderly. It is important to persevere and to use the prescribed drug at the correct dosage for long enough.

Patients often feel significantly better after two to three months on antidepressants, but it is important that medication be continued for as long as one’s doctor advises. For a first episode of depression this usually means taking medication six to nine months on optimal dosage after symptom relief has been achieved, two to five years for a subsequent episode and possibly life-long if episodes recur frequently and are severe. Stopping medication too soon increases the likelihood of relapse and the development of a chronic recurring illness.

The different types of antidepressants

1. Selective Serotonin Reuptake Inhibitors (SSRI’S)

These are among the newer antidepressants, which have been available from 1988. They act on the neurotransmitter (brain chemical) serotonin. Some of the trade names in this class include Aropax (paroxetine), Prozac, Lorien, Nuzak, Lily-Fluoxetine (fluoxetine), Cipramil, Cilift (citalopram), Cipralex, Lexamil (escitalopram), Zoloft, Serdep, Serlife (sertraline) and Luvox (fluvoxamine). This group of drugs, together with the other newer agents, is the most widely prescribed, due to their favourable side-effect profile and relative safety if taken in overdose. Different drugs in this class are also registered for treatment of anxiety disorders, panic disorders, post-traumatic stress disorders, obsessive-compulsive disorder and social phobia.

Side effects may be present during the first few weeks of therapy, but usually disappear after a while. These are often diminished by starting medication in low dosages and gradually increasing until a therapeutic dosage is reached.

Common side-effects include:

•    Nausea – (take after food)
•    Headache – (improves after a while; start with low dosages)
•    Agitation/anxiety
•    Sleep disturbances
•    Decreased appetite
•    Sexual disturbances (sexual problems may change, but if worrisome discuss with your doctor as treatment options are available)

2. SNRI (Serotonin and Noradrenaline Reuptake Inhibitors)

This class of medications is closely related to the SSRI’s, but have an additional mechanism of action in that they also affect noradrenaline reuptake. There are two medications in this class available at present, namely venlafaxine (Efexor, Venlor) and duloxetine (Cymbalta,CymGen). There is some evidence that this class of medications may be more effective in preventing relapse episodes of depression. They are also used when the depression is accompanied by painful physical symptoms such as headaches and muscle pain. Their side-effect profile is similar to that of the SSRI’s.

3. Tricyclics

This is an older group of drugs, which has been in use since 1957. These drugs affect predominantly noradrenaline. Some of the drugs in this class include Tryptanol, Trepiline (amitriptyline); Tofranil, Ethipramine (imipramine); Anafranil (clomipramine); Emdalen (lofepramine); Aventyl (nortriptyline) and others. Tricyclics are also used for the treatment of anxiety disorders, sleep disorders, pain relief, migraine prophylaxis and bedwetting (imipramine). Some patients, particularly the elderly, find the side effects of these drugs more difficult to tolerate. Tricyclics are not safe in overdose, and in the event of more tablets being taken than prescribed, medical advice should be sought urgently. Despite the side-effect profile, tricyclics are extremely effective antidepressants.

Common side-effects include:

•    Dry mouth
•    Dizziness (due to decreased blood pressure – alleviated by standing up slowly)
•    Constipation
•    Blurred vision (this will usually go away with time, so new glasses or lenses are not necessary)
•    Drowsiness (less of a problem with imipramine and lofepramine)
•    Weight gain

These side effects are often transient and of nuisance value only. They may be managed by altering diet, water intake and rising slowly from a lying or sitting position.

4. Monoamine Oxidase Inhibitors (MAOI’s)

This is an older group of antidepressants, which is used less frequently today. These agents act by inhibiting an enzyme called monoamine oxidase, which usually breaks down serotonin, noradrenaline and dopamine in the brain. This results in an increase in these neurotransmitters, the deficiency of which is associated with depressive illness. However, certain foodstuffs containing tyramine (e.g. cheese, red wine, processed meats and many others) also require monoamine oxidase for their metabolism. The inhibition of this enzyme results in an excess of tyramine which acts upon the blood vessels to cause a rise in blood pressure. This rise may sometimes be fatal, and hence patients taking MAOI’s need to observe dietary restrictions. The danger of any food or drug reaction persists for about 14 days after ceasing treatment with a MAOI. A washout period is therefore required before starting a different antidepressant.

The only MAOI as described above that is available in South Africa is Parnate (tranylcypromine). There is a newer MAOI available, which does not completely inhibit the monoamine oxidase enzyme, and dietary restrictions are thus not that important. A severe hypertensive episode is much less likely and these drugs are only contra-indicated if the patient already suffers from uncontrolled high blood pressure. This drug is called Aurorix (moclobemide).

MAOI’s are thought to be particularly useful in treating atypical depression. They are also useful when depression is not responding to other drugs and in phobia and panic disorder.

Common side-effects include:

•    Headache – may be a warning sign of a severe increase in blood pressure
•    Dizziness
•    Agitation/nervousness
•    Insomnia
•    Sexual problems
•    Drug interactions – discuss all medications, including over-the-counter drugs, with your doctor before taking
•    Interactions with certain foods

Again, most of these side effects usually improve after taking the medication for a few weeks.

5. Other antidepressants

These antidepressants do not fit into the aforementioned groups and many of them are newer agents.

•    Edronax (reboxetine) – launched in South Africa during 2000. This inhibits noradrenaline reuptake and there is more neurotransmitter available in the synaptic cleft. It is generally considered to be an energising antidepressant. It may cause insomnia, dry mouth, vertigo, sweating and some sedation initially. Not a good choice if there is a high level of anxiety associated with the depression.
•    Lantanon (mianserin) – classified as a tetracyclic. Affects noradrenaline but via a different mechanism to the tricyclics. This is a sedative antidepressant, which is taken at night – useful if insomnia is a prominent complaint. Also useful if low blood pressure is a problem as it tends not to exacerbate this, unlike the tricyclics. May cause weight gain.
•    Molipaxin (trazodone) – a triazolopyridine antidepressant unrelated to any of the aforementioned antidepressants. It affects the serotonin neurotransmitter system working on pre- and postsynaptic neurones (SSRI’s exert their effects on presynaptic neurones only). The main side effect is sedation. Priapism (sustained penile erection) has been reported and may result in irreversible impotence, but this is not a common side effect.
•    Remeron (mirtazapine) – belongs to a new class of antidepressant called NaSSA’s (noradrenergic and specific serotonergic antidepressants) which are particularly useful if anxiety and insomnia are problems. Side effects include sedation and weight gain.
•    Novel anti-depressants – a new anti depressant was launched in South-Africa in 2011. This medication, agomelatine, utilizes a novel mechanism by adressing circadian rhythms.

Some general points regarding antidepressants

It is important to inform your prescribing doctor of the following:

•    Any known illness, especially cardiac problems, epilepsy, diabetes, thyroid disease, liver disease, prostrate problems, glaucoma and high blood pressure
•    Any other medication which you may be taking. Ask your doctor or pharmacist about potential drug interactions before taking any other prescribed or over-the-counter medication, e.g. cough syrup, beta-blockers, anti-histamines, antacids.
•    Pregnancy or plans to fall pregnant in the near future and also if you are breast-feeding. Some medications can affect your baby.

It is also a good idea to try and avoid alcohol while taking antidepressants. Alcohol acts as a central nervous system depressant and can worsen depression or undermine the benefits of the medication. It also increases the likelihood of drowsiness and hence the risk for accidents while driving or operating machinery.

Electroconvulsive therapy (ECT)

It is not known exactly how ECT works, but it remains the most effective treatment for severe depression. The brain displays similar changes after ECT as after taking antidepressant medication, but the onset of improvement is more rapid with ECT.
ECT is a treatment which involves electrical stimulation of the brain while under a general anaesthetic. A muscle relaxant is also given before treatment is initiated. Because of bad publicity (films such as “One flew over the cuckoos nest”) and general anxiety about using electricity near the brain, it is a much underused therapy.

As a general anaesthetic is required, it is only reserved for severe depression or treatment-resistant depression or when a rapid improvement is important (as in post-natal depression which responds particularly well to ECT) and where physical health is good enough for an anaesthetic. ECT is also useful for patients who cannot tolerate the side effects of medication (such as the frail, elderly and pregnant women). Several ECT sessions are required for full therapeutic benefit, usually at a rate of three per week.

Self-help

Self-help is not a treatment for a depressive illness on its own, but it can contribute towards accelerating recovery and it can help to maintain the benefits of treatment.

Self-help includes:

•    Reading books/acquiring information. This helps to provide an understanding of the illness which can be important for both the sufferer and the family.
•    Eating an adequate diet, so as to maintain blood sugar levels. Foods, which promote serotonin production, can be increased e.g. bananas, pumpkin pips and Horlicks. Stimulants which increase anxiety should be avoided e.g. coffee, colas and chocolate. Vitamin supplements/tonics may be useful if you are very run down, or if life is normally lived in the “fast lane”. Consider taking omega-3 fatty acids, particularly EPA.
•    Sleeping sufficiently – but not too much.
•    Exercise – begin gradually and slowly increase the intensity and amount of time spent exercising. There is considerable evidence to show that exercise can have a profoundly positive effect on mood in people with depression. Being out in the fresh air also helps to put a different perspective on problems.
•    Relaxation – to decrease tension and anxiety and to improve sleep. E.g. meditation, yoga, aromatherapy and massage.
•    Hobbies/interests – which help to occupy the mind and decrease pre-occupation with negative thoughts.
•    Regular breaks/holidays
•    Life-style changes – expecting less of oneself; maybe lowering standards a little; delegating; asking for assistance.
•    Avoid alcohol/recreation drugs and cigarettes – these often worsen depression and anxiety.

Course

About half of patients who are diagnosed with a Major Depressive Disorder have had significant symptoms prior to the first diagnosed episode. In some the symptoms may be experienced fairly suddenly or acutely while in others there may be a long prodrome, and it is only retrospectively that changes in mood, behaviour and functioning are recognised.

An untreated depressive episode lasts from 6 – 13 months with the average duration being around 9 months. Most cases will improve, although a significant minority go on to develop a chronic depressive illness. Most treated episodes last about three months. However, medication should be continued for longer (six to nine months for a first episode), because withdrawal from medication too early is almost always associated with a relapse in depressive symptoms.

As mentioned previously, it is believed that the first episode in a mood disorder brings about long lasting changes, which increase susceptibility to subsequent episodes. It is also thought that if the initial episode is treated early enough, with adequate medication and for long enough, some of these changes may be prevented.

About 5 – 10 percent of patients who have initially been diagnosed with a MDD will experience a manic episode 6 – 10 years after the first depressive episode. The average age for that switch is 32 years and it usually occurs after two to four episodes of depression.

Prognosis

Major Depressive Disorder is a recurrent illness. While each episode usually responds to treatment it tends to be a chronic disorder and patients do tend to relapse (i.e. condition deteriorates again before an episode is completely resolved).

Recurrences of major depressive episodes are also common and for a patient who has required hospitalisation for the initial episode (i.e. severe depression). There is a 30 – 50 percent chance of recurrence within the first two years and a 50 – 75 percent chance of recurrence within five years. The likelihood of relapse or recurrence is much less in those who continue to use prophylactic psychopharmacological treatment (i.e. either continue with antidepressant medication or make use of a mood stabilising drug).

Usually as more depressive episodes are experienced, the time between episodes decreases and the severity of the depression increases. Men are more likely than women to experience a chronically impaired course. A poor prognosis is also more likely with a co-existing anxiety, dysthymic or substance abuse disorder.

Prevention

One cannot alter a genetic vulnerability or a history of loss, but much can be done to decrease stressors (see self-help). A balanced life-style with adequate social interaction and support, and knowledge of what comprises depression, so that help can be sought at the right time, can all help to prevent depressive episodes.

(Previously reviewed by Dr Piet Oosthuizen, Dept. Psychiatry, University of Stellenbosch, January 2008)

(Reviewed by Dr Stefanie van Vuuren, Psychiatrist, MB ChB (Stell), M Med (Psig) (Stell), FC (Psych)SA, May 2011)