What it is

Depression is the fourth most commonly managed problem in general practice in Australia. Most depressed patients who present to the GP have major depression with symptoms of mild to moderate severity; their presenting complaint might not be unhappiness. They often meet fewer of the criteria for major depression than those seen in psychiatric clinics.

Depressed patients often have coexisting mental and physical disorders which should be addressed in the management plan. For example, over half of patients with depression have at least one other mental disorder such as anxiety disorders and substance abuse disorders.


DSM-IV criteria for major depression
A. At least five of the following symptoms for at least two weeks (symptom 1 or 2 must be present):
1. Depressed mood
2. Loss of interest or pleasure
3. Significant appetite or weight loss or gain
4. Insomnia or hypersomnia
5. Psychomotor agitation or retardation
6. Fatigue or loss of energy
7. Feelings of worthlessness or excessive guilt
8. Impaired thinking or concentration; indecisiveness
9. Suicidal thoughts/thoughts of death

B. The symptoms cause clinically significant distress or impairment in social, occupational or other important areas of functioning.
C. Do not include symptoms that are clearly due to a general medical condition.

How to Treat

Before starting treatment:
- Exclude treatable causes (eg alcohol/illicit drug misuse, hypothyroidism, corticosteroid use)
- Consider using a structured assessment tool (eg Hamilton Depression Rating Scale) to document extent and nature of signs and symptoms for later assessment of treatment response.
- Obtain a baseline ECG and electrolytes if intending to use a TCA in children or if there is pre-existing cardiac disease.
- Measure standing and sitting BP, especially if considering use of TCA.
- Carefully review all current medications including non-prescription drugs, eg St John's wort, and assess potential for interaction.

Non-pharmacological strategies that might be applied in general practice include:
- support, understanding, encouragement and explanation
- meeting with other members of the family or friends
- advising environmental change
- recommending self-help groups
- contacting governmental and other agencies (e.g. housing departments) on behalf of the patient
- helping the patient with problem-solving skills
- discussing chronic social difficulties with the patient.
More formal psychotherapies such as cognitive behavioural therapy (CBT) are often useful.

Pharmacological strategies:
Current Australian guidelines recommend the newer antidepressants as first-line agents for treating major depression due to their more tolerable side effect profiles. However, because patients vary widely in how they respond to different agents, older and newer agents should be considered as possible options for therapy. Do not use more than one antidepressant concurrently.

TCAs, SSRIs, controlled release venlafaxine, mirtazapine and moclobemide are all regarded as first line drugs in adults. Nonselective MAOIs are generally reserved for patients with previous good response to them, or when other treatments are ineffective or not tolerated.

In children and adolescents: SSRIs are the drug of choice; TCAs are not better than placebo in this age group.

Factors influencing drug selection
The patient's past history of response to antidepressants, including allergies and intolerance
Consider as first-line therapy antidepressant agents that have previously been successful in treating the patient.
The nature and severity of depression
TCAs may be more effective in severely depressed patients who are more tolerant of adverse effects than mild to moderately depressed patients.
The patient’s concurrent medical and psychiatric history
Patients with chronic pain may benefit from a TCA; patients with obsessive-compulsive symptoms may benefit from an SSRI or clomipramine.
The pharmacological and adverse effect profiles of different antidepressant agents
Consider the adverse event profile of different drugs to individualise the patient’s therapy, eg consider a more sedating drug if insomnia or agitation are prominent
The potential for drug interactions with concurrently administered medications
SSRIs and nefazodone inhibit cytochrome P450 enzymes involved in the metabolism of other drugs
Toxicity in overdose, as well as the likelihood that the patient will attempt a deliberate overdose
Choose a newer agent which is less toxic in overdose than the TCAs or MAOIs, or supply only limited quantities of an older agent.
When switching between antidepressants, allow time for adequate drug clearance before commencing a new agent. There are two important safety issues:
1. avoiding the serotonin syndrome
2. preventing problems due to the inhibitory effect of the SSRIs and nefazodone on cytochrome P450 enzymes.
A guide to washout periods is found here (page 8)

Other advice

- To minimise adverse effects with all antidepressant agents, start at a low dose and increase over one to two weeks if the patient is tolerating the therapy
- Many adverse effects of antidepressants (e.g. nausea with selective serotonin reuptake inhibitors [SSRIs] or sedation with tricyclic antidepressants [TCAs]) settle within the first one or two weeks of treatment.
- Warn the patient that there is a delay between two and four weeks (longer in elderly people) before a noticeable antidepressant effect occurs.
- In patients who respond, maximum benefit may not occur for six to eight weeks.
- If the patient is not showing some signs of improvement after four weeks of therapy, check whether an adequate dose of antidepressant has been used for an adequate duration and recheck compliance.

Additional Resources

ORG - What is Serotonin. contains information on serotonin and related health problems and solutions
NPS - Topics: Depression: contains links to all articles on NPS related to depression
NPS - Case Study: Managing Depression in General Practice: about a 72-year old, long-term patient
NPS - Managing Depression
NPS - Pharmacotherapeutic Management of Depression: contains questions when reviewing depression management; also some useful tables on medications, washout periods and interactions
NPS - Case Study: Depression in Primary Care: about a 38-year-old female lawyer
AMH - Depression
Notes from TG - Depression: talks about all the different medications
Lecture Notes:
Pharmacology 301