Managing depression (Prescribing Practice Review)
Published in MedicineWise News
Date published: About this date
- Use an effective drug treatment for at least 6 months in major depression.
- 4–6 weeks of drug treatment may be needed before an effect is seen.
- Depression-specific psychological therapies are first-line in mild depression and effective adjuncts in more severe depression.
- Ask about suicidal thoughts and assess risk, especially during initial treatment.
- Advise patients what to expect from drug therapy: likely adverse effects; time to effect; and the expected course of treatment.
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 suicide1–3
Table 1: Severity of depression and treatment recommendations1-3
|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|
|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
|More than minimum criteria met, greater degree of impairment to functioning||Drug treatment and depression specific psychological therapy have equal efficacy|
-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 depression1,2,5
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 therapy13
- in those with residual symptoms after a period of optimum drug treatment14
- 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 people18.
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
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.7,24Of all the TCAs, nortriptyline is least likely to cause hypotension, sedation or anticholinergic effects.
Assess suicide risk in patients with depression
Asking about suicidal thoughts does not cause suicidal behaviour25
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 questions1
'Have you got or had suicidal thoughts?'
'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 suicide1,25,26
Assess suicidal intent, but be aware that suicide risk is difficult, and protocols have low predictive value[1,25,27
The risk of suicide increases when the suicide plan is detailed, the method is readily available and likely to be lethal, and the plan minimises the possibility of help from others. The presence of aggressiveness, violence, hopelessness, impulsiveness or agitation are thought to be correlated with an increased risk of suicidal behaviours.25
Eliciting guarantees of safety or 'no self-harm' contracts are not recommended as sole management strategies.1
Some findings suggest that SSRIs may aggravate suicidal ideation in children and adolescents. These require further investigation but the Therapeutic Goods Administration has alerted practitioners to the possibility.28
Consider prescribing a drug that is less toxic in overdose and limit quantities dispensed
TCAs and monoamine oxidase inhibitors (MAOIs) are considered the most toxic in overdose.7 SSRIs are least toxic but consider the combinations of medicines that may be available to the patient.
Dr Bill Lyndon
Chairman of the RANZCP Committee on Psychotropic Drugs and Other Physical Treatments
- Therapeutic Guidelines: Psychotropic. Version 5, 2003.
- Ellis PM, et al. Med J Aust 2002;176 Suppl:S77–83.
- Royal Australian and New Zealand College of Psychiatrists. Aust N Z J Psychiatry 2004;38:389–407.
- Quitkin FM, et al. Arch Gen Psychiatry 1996;53(9):785–92.
- Anderson IM, et al. J Psychopharmacol 2000;14(1):3–20.
- Walsh BT, et al. JAMA 2002;287(14):1840–7.
- Australian Medicines Handbook 2004.
- McManus PM, et al. Aust N Z J Psychiatry 2004;38:450–4.
- Garfield S, et al. Pharmaceutical Journal 2004;272(7298):576–7.
- Demyttenaere K, et al. J Clin Psychiatry 2001;62 Suppl 22:30–3.
- Bower P, et al. Psychol Med 2003;33(2):203–15.
- King M, et al. Health Technol Assess 2000;4(19):1–83.
- Jarrett RB, et al. Arch Gen Psychiatry 2001;58(4):381–8.
- Paykel ES, et al. Arch Gen Psychiatry 1999;56(9):829–35.
- Ludman E, et al. Psychol Med 2003;33(6):1061–70.
- Pampallona SB, et al. Arch Gen Psychiatry 2004;61(7):714–9.
- Proudfoot J, et al. Psychol Med 2003;33(2):217–27.
- Christensen H, et al. J Med Internet Res 2002;4(1):e3.
- Wilson K, et al. Antidepressant versus placebo for depressed elderly (Cochrane Review). In: The Cochrane Library, Issue 2, 2004.
- Hall M, et al. Aust Prescr 2003;26:62–3.
- Adverse Drug Reactions Advisory Committee. Hyponatraemia with SSRIs. Australian Adverse Drug Reactions Bulletin 2003;22(3).
- Fabian TJ, et al. Arch Int Med 2004;164(3):327–32.
- Drug & Therapeutics Bulletin 2004;42(3):17–8.
- Davies SJ, et al. BMJ 2004;328:939–43.
- American Psychiatric Association. Practice guideline for the assessment and treatment of patients with suicidal behaviors. Am J Psychiatry 2003;160(11 Suppl):1–60.
- Mental Health Branch, Commonwealth Department of Health and Family Services. Youth suicide in Australia. 2nd edition. Australian Government Publishing Service; 1997. Available at www.mentalhealth.gov.au/resources/nysps/pdf/mhb32.pdf (accessed July 2004).
- Boyce PC, et al. Australasian Psychiatry 2003;11(2):150–5.
- Adverse Drug Reactions Advisory Committee. Use of SSRI antidepressants in children and adolescents—updated 17 June 2004. Available at ww.tga.gov.au/adr/adrac_ssri.htm (accessed July 2004).