Before contemplating treatment, you should have taken a full history of the patient along with a comprehensive physical examination. Relevant investigations should be completed and a thorough risk assessment undertaken. Your risk assessment will guide the treatment setting — community, home treatment team, or inpatient. The risk of suicide will also govern the choice and quantity of antidepressants prescribed at any one time.
The treatment of depression should follow a Stepped Care Model, as recommended by NICE. Assessment and diagnosis are usually carried out by the GP or practice nurse. Some surgeries have primary mental health workers attached to them who can guide and support treatment. Mild to moderate depression is generally treated in primary care, while severe depression is managed in secondary or tertiary care.
Categories of Treatment
1 — Biological Treatments
- Antidepressants
- Mood stabilisers (in specific cases, e.g. bipolar depression)
- Electroconvulsive Therapy (ECT)
2 — Psychological Treatments
- Guided self-help
- Problem-solving therapy
- Counselling
- Interpersonal Therapy (IPT)
- Cognitive Behavioural Therapy (CBT)
The above treatment modalities represent the most commonly used options. For a comprehensive overview, refer to a standard psychiatry textbook.
Mild Depression
Antidepressants are not advocated as first-line treatment in mild depression, as the risk-benefit ratio is poor at this severity level.
Watchful waiting is advised initially, but it may be necessary to provide counselling or problem-solving therapy. Patients can also be offered computerised CBT with self-help guides. Information on sleep hygiene, anxiety management, and substance misuse may also be relevant. The patient should be followed up regularly to monitor for signs of improvement or deterioration, with a risk assessment undertaken at each contact.
Moderate Depression
An antidepressant should be started. The choice depends on patient characteristics including physical health, risk of suicide, substance misuse history, expected adverse effects, and — most importantly — patient choice and preference.
Generally, an SSRI (Selective Serotonin Reuptake Inhibitor) such as sertraline or fluoxetine is the first-line drug of choice. SSRIs are safer with regard to frequency of side effects and in overdose compared with older antidepressant classes.
Patients should be monitored regularly for side effects, deterioration in mood, and suicidal ideation. They should always be seen within one week of starting antidepressants, and a risk assessment should be carried out at each review. Information about sleep hygiene, anxiety management, and substance misuse is valuable.
If patients do not respond to the initial antidepressant, switch to another agent from the same class or from a different class. Tricyclic Antidepressants (TCAs) are one of the oldest classes and are effective, but their use has declined due to side effects and significant toxicity in overdose. Other options include the newer antidepressants such as mirtazapine, reboxetine, or venlafaxine.
Psychological therapies are also an important component of treatment. CBT and IPT, delivered by trained healthcare professionals for a period of at least 6 months, are recommended by NICE.
Severe Depression
Severe depression can sometimes be treated in primary care, but it is more often managed in secondary care as an outpatient, or in tertiary care by a home treatment team or as an inpatient, depending on the degree of risk.
The best evidence supports using both pharmacological and psychological treatments together. Pharmacological treatment follows the same principles as for moderate depression — starting with an SSRI and progressing to other classes if there is no response. In cases of agitated depression, a short course of a tranquilliser may be particularly useful in the initial period.
Monitor food and fluid intake carefully, and monitor suicidal ideation at every contact. Never prescribe more than one to two weeks' supply of medication at any one time in a patient at high risk.
Psychological treatment for severe depression should consist of CBT delivered by a trained professional for at least 6–9 months.
Resistant Depression
If depression has not responded to an adequate dose of antidepressant for an adequate duration, investigate the following:
- Non-compliance with medication
- Co-morbid substance misuse (alcohol or drugs)
- Social factors — relationship or financial difficulties that are hampering improvement (help should be provided in these areas)
- Occult physical causes — malignancy, space-occupying lesion in the brain, chronic pain, hypothyroidism, diabetes, and adrenal gland pathology
If the patient's condition is deteriorating with psychomotor retardation and they are not eating or drinking, discuss with your supervisor as this constitutes a psychiatric emergency — ECT may be one of the management options.
If no physical or social cause is identified, augmenting the antidepressant with another antidepressant, lithium, sodium valproate, or a low-dose antipsychotic can be useful. Augmentation strategies should be guided by the clinical supervisor, taking into account possible side effects and patient choice.
Treatment of Depression in Special Populations
Depression in Young People (Children and Adolescents)
Depression in children and adolescents should be treated by specialist Child and Adolescent Mental Health Services (CAMHS). Antidepressants are not routinely recommended as first-line treatment in this age group. The main treatment modalities are psychological, including family therapy and CBT. Social issues such as family discord, abuse, and bullying are often the main precipitating and perpetuating factors.
In severe depression, if CBT has been tried without adequate response, fluoxetine may be considered — it is the only SSRI licensed for use in children in the UK (from age 8 upwards). This should always be initiated under specialist supervision.
Depression in Older Adults
Depression in older age generally follows the same treatment principles as in adults. However, you must be more mindful of side effects — lower doses are generally used, and drug interactions are more common due to polypharmacy. Be vigilant for an underlying physical disorder or dementia contributing to the presentation. Older adults need more social care input, and treatment should always be multidisciplinary.
Depression in Pregnancy and the Perinatal Period
Depression is not uncommon in pregnancy. A multidisciplinary approach is essential, involving the midwife, obstetrician, and paediatrician. There must be a thorough discussion with the patient about risks to the foetus from medication, as well as considerations for breastfeeding. These discussions and decisions should be documented in as much detail as possible.
For mild to moderate depression, psychological treatments such as CBT or IPT are preferred. If there is no response, or the patient declines psychological treatment, antidepressants may be considered. TCAs such as amitriptyline or imipramine have the lowest known teratogenic potential but are more toxic in overdose. Sertraline and imipramine have lower concentrations in breast milk than most other antidepressants, making them preferable options during breastfeeding. All prescribing decisions should be guided by the current NICE Antenatal and Postnatal Mental Health guideline (NG216).
Depression with Cardiac Impairment
SSRIs such as sertraline or fluoxetine are generally considered safe in patients with established cardiac disease. Tricyclic antidepressants should be avoided, as they can prolong the QTc interval and cause arrhythmias. Always check the product literature and seek advice from cardiology colleagues if in doubt.
Depression with Renal Impairment
Fluoxetine and sertraline are the preferred options in patients with renal impairment. Doses may need to be reduced and renal function monitored regularly. Always consult with senior colleagues and check the current British National Formulary (BNF) before initiating treatment.
Depression with Hepatic Impairment
Lower doses of antidepressants are required, with careful monitoring of liver function and side effects. Look out for co-morbid alcohol misuse, which is both a cause and a consequence of hepatic impairment. Always seek advice from senior colleagues before initiating treatment in patients with significant liver disease.
Key Antidepressant Pharmacology
The following is a summary of the main antidepressant classes and their pharmacological profiles to guide clinical decision-making:
| Drug / Class | Mechanism | Key Features |
|---|---|---|
| SSRIs (sertraline, fluoxetine, citalopram) | Selective serotonin reuptake inhibition | First-line; safe in overdose; initial GI side effects; sexual dysfunction; take 2–4 weeks to work |
| Venlafaxine (SNRI) | Serotonin and noradrenaline reuptake inhibition | Useful in treatment-resistant cases; monitor BP; can raise blood pressure at higher doses; discontinuation syndrome |
| Duloxetine (SNRI) | Serotonin and noradrenaline reuptake inhibition | Less cardiac risk than venlafaxine; also licensed for generalised anxiety disorder and neuropathic pain |
| Mirtazapine (NaSSA) | Alpha-2 antagonist; 5-HT2 and 5-HT3 antagonist | Sedating; useful for insomnia; increases appetite; weight gain common; good for agitated depression |
| TCAs (amitriptyline, imipramine) | Non-selective monoamine reuptake inhibition + anticholinergic effects | Effective but toxic in overdose; anticholinergic side effects; avoid in cardiac disease; useful in chronic pain |
| MAOIs (phenelzine, tranylcypromine) | Irreversible monoamine oxidase inhibition | Rarely used; require tyramine-free diet; multiple drug interactions; specialist use only |
Frequently Asked Questions
What is the stepped care model for depression?
The NICE stepped care model organises treatment in increasing levels of intensity based on the severity of depression. Step 1 (all levels): recognition, assessment, psychoeducation, active monitoring. Step 2 (mild to moderate): low-intensity psychological interventions — guided self-help, computerised CBT, exercise programmes. Step 3 (moderate to severe or persistent mild): high-intensity psychological treatment (CBT, IPT), antidepressants, combined treatments, collaborative care. Step 4 (severe, complex, or high risk): specialist mental health services — crisis teams, inpatient care, ECT, complex pharmacological strategies. Each step builds on the previous, and patients can move up or down depending on response.
What is the difference between venlafaxine and duloxetine?
Both venlafaxine and duloxetine are SNRIs (serotonin and noradrenaline reuptake inhibitors). Venlafaxine is dually active at serotonin and noradrenaline receptors at higher doses, and may raise blood pressure — cardiac monitoring is advised. Duloxetine inhibits serotonin reuptake approximately 5 times more potently than noradrenaline, has less cardiovascular risk, and is also licensed for generalised anxiety disorder and diabetic peripheral neuropathy. Both are useful in treatment-resistant or complex depression, and both should generally be initiated or supervised by secondary care.
What does ECT involve and when is it used in depression?
Electroconvulsive Therapy (ECT) involves passing a controlled electrical current through the brain under general anaesthesia to induce a brief seizure. It is a safe and highly effective treatment with a strong evidence base. ECT is indicated in severe depression when there has been failure to respond to two or more adequate antidepressant trials; where there is severe psychomotor retardation with failure to eat or drink (a life-threatening emergency); where the patient has severe suicidal intent; or in depressive stupor. It is always a specialist decision, requiring informed consent and — where capacity is lacking — assessment under the Mental Capacity Act or Mental Health Act.
How should antidepressants be switched if the first one fails?
When switching antidepressants, consider a cross-taper — gradually reducing the first drug while slowly introducing the second — to minimise discontinuation symptoms and reduce the risk of gaps in treatment. The specific switching strategy depends on the combination of drugs. For example, switching from one SSRI to another can usually be done with a direct switch or a short cross-taper. Switching from an SSRI to an MAOI requires a washout period (14 days for most SSRIs; 5 weeks for fluoxetine due to its long half-life). Always consult the BNF and/or the Maudsley Prescribing Guidelines for specific switching protocols.
Is fluoxetine safe in children with depression?
Fluoxetine is the only SSRI licensed in the UK for use in children aged 8 years and over with depression. It should only be used when psychological therapies (primarily CBT) have been tried and have not produced adequate improvement. It must be initiated and monitored by specialist CAMHS services, not in primary care. All other SSRIs — including sertraline, citalopram, and escitalopram — are not licensed for depression in children and adolescents, and paroxetine is specifically contraindicated in this age group.
What are the safe antidepressant options during breastfeeding?
Sertraline is generally considered the preferred antidepressant during breastfeeding, as it has low levels in breast milk and extensive safety data. Imipramine (a TCA) also has relatively low milk concentrations. Fluoxetine is less preferred during breastfeeding due to its long half-life and higher milk concentrations. Paroxetine has low breast milk transfer but is associated with neonatal discontinuation syndrome. All prescribing decisions must balance maternal benefit against infant risk, should involve the patient in shared decision-making, and should be documented carefully in the notes.
What is the role of lithium augmentation in resistant depression?
Lithium augmentation — adding lithium to an existing antidepressant — is one of the best-evidenced strategies for treatment-resistant depression. It is typically tried after failure of two adequate antidepressant trials. Lithium has a narrow therapeutic index (target serum level 0.6–1.0 mmol/L for augmentation; 0.8–1.0 mmol/L for mood stabilisation). Regular monitoring of serum lithium levels, renal function (eGFR, urea, creatinine), thyroid function, and ECG is mandatory. Lithium should only be initiated and supervised by a consultant psychiatrist.
References
- National Institute for Health and Care Excellence. Depression in adults: recognition and management. NICE Clinical Guideline CG90. NICE, 2009 (updated 2022). Available at: nice.org.uk/guidance/cg90
- Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357–1366.
- National Institute for Health and Care Excellence. Depression in children and young people: identification and management. NICE Guideline NG134. NICE, 2019.
- National Institute for Health and Care Excellence. Antenatal and postnatal mental health: clinical management and service guidance. NICE Clinical Guideline CG192 (updated as NG216). NICE, 2014.
- Stahl SM. Essential Psychopharmacology: The Prescriber's Guide. 6th ed. Cambridge University Press, 2017.
- Taylor D, Barnes TRE, Young AH. The Maudsley Prescribing Guidelines in Psychiatry. 14th ed. Wiley-Blackwell, 2021.
- Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder. Can J Psychiatry. 2016;61(9):510–523.