Assess the severity of depression to determine whether drug treatment is required

Drug treatment guidelines are based on evidence in people with major depression

Severity of major depression depends on the

• number of depressive symptoms

• degree of impaired functioning

• history of depression

• risk of suicide[1–3]

Table 1: Severity of depression and treatment recommendations [1-3]

Type of depression and severity	Diagnosis*	Treatment recommendations
Milder depression or adjustment disorder†	Do not meet criteria for major depression	Little evidence to guide treatment choices May resolve spontaneously or with supportive psychotherapy, counselling, or problem-solving
Chronic Milder depression (dysthymia)	Repeated episodes if milder despression that do not meet criteria for majot depression	Antidepressants can be effective but response is unpredictable
Major depression -mild	Meet minimum criteria for major depression	Initial drug therapy not well supported by evidence Consider supportive therapy or problem-solving techniques, or CBT If symptoms persist beyond 8 weeks, consider drug treatment
Major depression -moderate	More than minimum criteria met, greater degree of impairment to functioning	Drug treatment and depression specific psychological therapy have equal efficacy
Major depression -severe of with high suicide risk	Most deagnositic criteria met Marked impairment in ability to function	Consult with or refer to specialised mental health services/psychiatrist

^{*Major depression diagnosed according to DSM-IV - see Therapeutic Guidelines Psychotropic 2203 [1]}

^{†Adjustment disorder refers to depressed mood in response to a stressful life event (e.g.bereavement)}

4–6 weeks of drug treatment may be needed before an effect is seen

Use response after 4–6 weeks to guide ongoing management

During initial treatment, follow up to encourage medication use and adjust treatment as necessary

Although no drug or class is more efficacious than any other, it is estimated that only 50% of patients respond to initial drug treatment.[1]

If there is no response after 4–6 weeks, response is unlikely.[1,4,5] (Note that older people should be started at a lower dose and may take longer to respond).

If there is a partial response after 4–6 weeks, then a longer trial or increased dose of the same drug is reasonable. However note the following.

• In antidepressant trials, around 50% of patients respond to active treatments in the first 4–6 weeks of treatment. However 30% of patients on placebo respond to a similar degree.[6] Such effects may account for early but unsustained improvement.
• Higher doses of selective serotonin reuptake inhibitors (SSRIs) increase adverse effects with uncertain benefit.[7] It is prudent to remain within doses recommended in the drug’s product information.

If response to an adequate trial of the initial medication is poor, switching to a different drug class is recommended after checking compliance.[1] If depression persists after 3 months of therapy, consider
referral or consultation with a specialist colleague.[2] Consider adjunctive psychological therapy.

Use antidepressants for at least six months in major depression to prevent relapse or recurrence 

Continued drug therapy for 6–12 months is recommended for all episodes of major depression[1,2,5]

Only 40% of patients in Australia who start on an antidepressant* are still using antidepressants 6–8 months later.[8]

Aim to achieve a stable symptom-free period of 4–6 months before the depression is considered to be in remission. Suboptimal treatment durations increase the likelihood of relapse or recurrence.[1,2,5]

Maintenance doses should be the same as doses used to achieve initial control.[1,2,5]

A history of depression increases the likelihood of relapse and recurrence

For first episodes of major depression, continue antidepressant treatment for 6–12 months.[1,2,5]

As depression is a relapsing condition, ask about previous episodes in any patient presenting with a new episode.[2] Patients with a history of major depression and/or chronic milder depression (dysthymia) have a higher risk of relapse or recurrence than those with a single episode of major depression.

Guidelines suggest that 2 episodes of major depression within 5 yearsor 3 prior episodes may indicate a need for maintenance treatment of 3–5 years.[1]

^{* Note: This includes antidepressants prescribed for other problems, including milder depressive illness.[8]
Recommended treatment durations are based on evidence for major depression.}

Medication advice can improve compliance and outcome

Be aware of possible reasons that patients stop treatment early

Provide advice about what to expect from medications, address concerns and follow up to improve compliance

Address potential concerns about adverse effects, lack of effect, perceived stigma of antidepressant drug use, and educate patients about duration of treatment.[9,10] Advise patients that

• adverse effects may occur—what these are and their expected duration
• mood may not improve immediately
• not all people respond to the first drug chosen, and there are other treatment options
• missing doses may reduce effectiveness
• even when they feel better, they should continue drug treatment for at least 6 months
• drugs should not be ceased abruptly, but tapered gradually because of possible ‘rebound’ symptoms.

Follow-up patients to monitor for adverse effects and to support compliance—this may improve treatment adherence.[2]

Psychological treatments are effective for many patients with depression

Consider psychological therapy as initial treatment in mild depression or as an adjunct to drug therapy in more severe depression

Non-drug interventions in depression range from supportive counselling, education and information, through to more structured depression-specific psychological therapies.

Non-directive counselling may reduce symptoms in the short-term and is associated with patient satisfaction.[11,12]

Specific psychological therapies such as cognitive behavioural therapy (CBT) and interpersonal therapy (IPT) are recommended as:[2]

• first-line treatment for mild or moderate depression
• adjunctive therapy if response is not achieved with a drug alone (in moderate to severe major depression)
• preventive therapy to prevent recurrence when a patient is in remission.

Psychological therapy may prevent relapse

Specific cognitive therapies have been shown to prevent relapse

• after successful acute treatment with cognitive therapy[13]
• in those with residual symptoms after a period of optimum drug treatment[14]
• and in patients with a high risk of recurrence.[15]

There is limited evidence comparing combined treatment (antidepressants plus psychological therapy) with antidepressant drugs and usual care. However a recent review found that drugs-plus-psychotherapy was associated with an increased likelihood of response and a decreased likelihood of long-term dropout than drugs alone.[16]

If access to psychological services is problematic, look into low-cost programs or other delivery  options 

Cost, availability and patient preference may limit the use of psychological therapies. Consider:

• the range of options available through the Commonwealth-funded Better Outcomes in Mental Health Care Initiative including: low-cost or free access to approved psychological services, upskilling of GPs, new Medicare item numbers for trained GPs and service incentive payments. Contact your local division of general practice or visit Australian Divisions of General Practice (ADGP).
• computer based interactive CBT programs[17,18] that are being evaluated—for example MoodGYM, a free web-based intervention initially designed for young people[18].

Consider adverse effects and interactions when prescribing antidepressants to older people

Start at a lower dose and increase slowly

Both SSRIs and tricyclic antidepressants (TCAs) are effective treatments in late-life depression,[19] but SSRIs are generally first-line because they are better tolerated.

Selective serotonin reuptake inhibitors (SSRIs)

Of the SSRIs, fluoxetine, fluvoxamine and paroxetine have more potential drug interactions than sertraline or citalopram.

Be aware of the possibility of serotonin syndrome which can occur when multiple drugs are used which affect serotonin, or with high doses of a serotonergic drug (e.g. most antidepressants, tramadol, pethidine, buspirone, amphetamines and anorectics).[20]

Common adverse effects

Initial adverse effects include nausea, insomnia, drowsiness, dizziness and agitation. These usually resolve within a few weeks. Sexual dysfunction and weight gain may continue long-term and affect compliance.[7]

Less common adverse effects

The elderly are vulnerable to hyponatraemia related to SIADH (syndrome of inappropriate ADH secretion) with SSRIs or venlafaxine. Being female, having a lower BMI and a lower baseline sodium level appear to increase risk.[21,22] Adverse event reports have often noted concurrent use of thiazide diuretics.[21]

Decreases in plasma sodium levels can be seen within 2 weeks of starting
SSRIs.[22] Symptoms include confusion, lethargy and dizziness. Consider monitoring sodium levels during initial treatment.

There appears to be a small increase in the absolute risk of gastrointestinal bleeding (about 3 extra cases per 1000 patient-years of treatment) with SSRIs in patients aged ≥ 80 years, with previous gastrointestinal bleeding, or concurrent use of aspirin or another NSAID.[23]

Tricyclic antidepressants

TCAs are not first preference in older people because of their adverse effects—sedation increases the risk of falls. They should not be used in patients with cardiac disease due to their anticholinergic and proarrhythmic effects.[7,24] Of all the TCAs, nortriptyline is least likely to cause hypotension, sedation or anticholinergic effects.[7]

Assess suicide risk in patients with depression

Asking about suicidal thoughts does not cause suicidal behaviour[25]

Assessing the extent of the plan is an important part of assessing risk. Patients may be relieved to have the opportunity to discuss the issue.[25]

Key clinical questions[1]

'Have you got or had suicidal thoughts?’

If yes:

‘Have you ever made or got close to making a suicide attempt?’

‘Have you ever made detailed plans?’

‘Do you feel you can keep in control of your suicidal thoughts?’

Risk factors for suicide[1,25,26]

A previous suicide attempt or acts of self harm Being male Access to means of suicide (tablets, firearms) Social Isolation Chronic medical illness Young people and older people have higher risks of suicide

Diagnosis of: major depression bipolar disorder schizophrenia or schizoaffective disorder alcohol/drug abuse personality disorder current psychosis

 

Expert reviewers

References

1.