The British Association for Psychopharmacology
These guidelines are primarily concerned with the use of antidepressant drugs to treat the most common mild to moderate depressive states in adults and do not cover depressive disorders occurring in bipolar affective (manic-depressive) disorder or associated with psychotic symptoms.
Depression
Depression is a common illness. The weekly prevalence of major depression in the UK is reported to be 2.3 per cent and that of milder depressive states 7.7 per cent. Rates are more approximately two to three times higher in women than men. Dysthymia has been reported to have an annual prevalence rate of 2.5 per cent.
In general practice 5 to 10 per cent of consecutive patients have major depression and a similar number have milder depressive states. Between 30 and 50 per cent of cases of depression in primary care and medical settings are not detected.
Why depression is missed
The patient
- Fearing the stigma of psychiatric illness
- Not recognising that they have an illness
- Not knowing that depression can be treated
- Fearing the side effects of medication
The physician
- Lack of skills or time to detect depression
- May be missed by physical complaints
- Perception of depressive symptoms as 'understandable' reactions to circumstances
- May avoid the diagnosis through lack of skills, time or belief in treatment.
Recent trends show that antidepressant prescribing by primary care physicians is increasing but the impact of this on the outcome of depressive disorders is unknown.
Detection
Improving the outcome of major depression requires a multi-faceted approach including:
- Education of public and doctors about the detection and treatment of depression
- Adoption of clinical guidelines for treatment
- Restructuring service provision to ensure that the guidelines are applied
Diagnosis
Major depression
A diagnosis of major depression can be made when five or more of the core symptoms have been present for at least two weeks, one of which must be depressed mood or loss of interest or pleasure.
The core symptoms are:
- Depressed mood
- Loss of interest or pleasure in almost all activities
- Significant weight loss or gain or changes in appetite nearly every day
- Sleep disturbance
- Agitation or retardation (observable by others)
- Loss of energy or fatigue
- Feelings of worthlessness or self blame
- Concentration difficulties
- Recurrent thoughts of death or suicidal thoughts
The criteria for diagnosis also require that the symptoms cause clinically significant distress or impairment in functioning, and that they are not better explained by bereavement.
Milder depression does not meet full syndromal diagnosis for major depression and is often associated with significant anxiety symptoms. This category often includes bereavement and adjustment disorders.
Dysthymia is a chronic depressive state (defined as greater than two years' duration) which does not meet full criteria for major depression and is not the consequence of a partly resolved major depression.
Depressive states often co-exist with physical illness and other psychiatric disorders, notably alcohol and drug misuse, anxiety and obsessive-compulsive disorders and eating disorders in women.
Suicide Risk
- Suicide risk should be considered at all stages of presentation and treatment - suicidal ideation may develop for the first time during treatment and up to a third of depressed patients committing suicide have received antidepressants.
Referral
Referral to psychiatric services is indicated for the following:
- Risk of suicide
- Psychotic symptoms
- History of bipolar affective disorder
Consultation with, or referral to, a psychiatrist is appropriate:
- When the practitioner feels insufficiently experienced to manage a patient's condition
- If two or more attempts to treat the patients depressive disorder have failed or resulted only in partial response
Treatment with antidepressants
- Antidepressants are indicated as a first line treatment for major depression including that associated with physical illness. Prior life events do not reduce the response to antidepressants but increase the response to placebo.
- Antidepressants appear to have increasing benefit over placebo as severity of depression increases, with the greatest separation in more severe cases. At the mildest severity the benefit is uncertain.
- Antidepressants are not indicated at initial presentation of acute milder depressions or very mild major depression. A trial of treatment is recommended in persistent milder depression.
- Treatment with antidepressants should be considered for milder depression if there is a history of major depression.
- Antidepressants are effective in the acute treatment of dysthymia and are a first line treatment.
- For most patients there is little to choose between individual antidepressants in terms of efficacy. Systematic reviews have suggested advantages to individual drugs/classes in certain situations:
- Tricyclic antidepressants (TCADs) may be more effective than SSRIs in patients hospitalised for major depression
- MAOIs may be more effective than TCADs in non-hospitalised patients with 'atypical depression' defined by mood reactivity and at least one associated symptom (increased appetite/weight gain, increased sleep, severe fatigue/leaden heaviness of limbs, sensitivity to rejection as a personality trait). However, dietary restrictions, tolerability and safety problems limit their use to second-line therapy.
- Venlafaxine, at a dose of 150mg or greater, may be more effective than SSRIs for major depression of at least moderate severity.
- Newer antidepressants are generally better tolerated than the older TCADs and are safer in overdose.
- SSRIs are more likely than older TCADs to be prescribed at recommended doses for an adequate period.
- Newer antidepressants are more expensive than older drugs but current pharmacoeconomic data do not favour initial treatment with one antidepressant over another.
Choosing and using antidepressants
- Choice of drug should be related to the individual patient.
- In the absence of special factors (see below), choose antidepressants which are better tolerated, safer in overdose and more likely to be prescribed at effective doses. There is most evidence for SSRIs with lofepramine, mirtazapine, nefazodone, reboxetine and venlafaxine also relatively safe and well tolerated.
- In situations where maximising efficacy is of overriding importance, consider an older TCAD or venlafaxine at 150mg or greater in preference to an SSRI or MAOI.
- Factors to consider in relationship to individual patients when prescribing an antidepressant:
- previous treatment response to a particular drug
- tolerability and adverse effects of a previously given drug
- likely side effect profile
- low lethality if history or likelihood of overdose
- concurrent physical illness or condition that may make the antidepressant more noxious or less well tolerated (eg, ischaemic heart disease, pregnancy)
- concurrent medication that may interact with the antidepressant drug
- associated psychiatric disorder that may specifically respond to a particular class of antidepressant (eg, SSRIs or clomipramine are indicated in obsessive-compulsive disorder)
- patient preference - Aim for a target dose for which there is established efficacy (usually 125mg or above for most older TCADs). Lower doses are usually recommended in the elderly. Increase the dose slowly when using less well tolerated antidepressants to allow adjustment to side effects. However, side effects may limit the dose that can be achieved.
- Following commencement of antidepressant treatment, patients should be reviewed every one to two weeks by suitably trained staff to assess response, compliance with drug treatment, side effects and suicidal risk.
- Educate patients about the nature of depressive disorders and the side effects and benefits of medication as this improves compliance.
- Limit the total amount of antidepressant drug available to the patient to reduce risk if taken in overdose.
Response and non-response
- Eventual response is unlikely if there is no improvement after four weeks; with partial improvement continue to six weeks before changing treatment (elderly patients may take longer to respond).
- If no response, review whether diagnosis is correct, whether there are concurrent physical or psychiatric conditions, and check whether initial treatment was adequate in terms of dose and compliance. Compliance with antidepressants is relatively poor, ranging from 40 to 90 per cent in different studies.
- Strategies with evidence for efficacy following initial non-response to treatment with an antidepressant are increasing the dose (limited evidence), switching drug, augmentation with lithium or tri-iodothyronine, ECT and adjunctive psychotherapy.
- It is important to continue drug treatment, at the same dose as in the acute phase, for a minimum of six months after initial remission of major depression as this has been shown to halve the relapse rate. Elderly patients should be treated for a minimum of 12 months.
Maintenance treatment
- Patients with recurrent major depression should go on to receive maintenance antidepressant drug treatment. New episodes of major depression are prevented by continuing treatment beyond six months in patients with at least three episodes in the past five years or more than five episodes altogether. The elderly may also benefit from longer treatment (limited evidence).
- The antidepressant should be continued at the same dose as used in acute treatment and continued for at least five years and possibly indefinitely.
- Lithium is a second-line alternative to antidepressants for maintenance treatment.
Stopping treatment
- A discontinuation reaction may occur if treatment is stopped abruptly after a few weeks' treatment and patients should be warned about this when treatment is started.
- When stopping antidepressants taper dose (or frequency) over a minimum of four weeks if possible. Taper over six months after long term maintenance treatment.
- Discontinuation symptoms differ in pattern from those of depressive relapse. Common symptoms include:
- balance and sensory disturbance
- gastrointestinal symptoms
- insomnia and mood abnormalities - Most discontinuation reactions are mild and are appropriately treated with education and reassurance. If it is severe, the drug should be restarted and tapered more slowly.
Full guideline available from:
The British Association for Psychopharmacology, Lower Ground Floor, 6 Regent Terrace, Cambridge CB2 1AA. Tel: (01223) 358395
Evidence-Based Guidelines for the Treatment of Depressive Disorders with Antidepressants. Journal of Psychopharmacology (2000);14(1):3-20.
