UNDERSTAND
heterogeneity, context & biology

ASSESS
severity, risk, function & differential

TREAT
shared decisions & measurement-based care

UK clinical framework • International evidence • Patient-centred practice

A detailed evidence-informed guide to modern models of depression, clinical assessment, psychological and pharmacological treatments, physical therapies, lifestyle care, treatment resistance and emerging science.

Introduction

Depression is common, disabling and clinically diverse. It is not simply sadness, and it is not adequately explained by a single neurotransmitter deficit. The modern view is of a heterogeneous syndrome in which mood, reward, cognition, sleep, stress physiology, bodily symptoms, relationships and social context interact. Different people can meet criteria for depression through markedly different symptom patterns and causal pathways.

The most useful clinical question is therefore not only “Does this person have depression?” but also “What type of depressive presentation is this, what is driving or maintaining it, what risks are present, and what is most likely to help this individual now?” Good care combines diagnostic assessment with formulation, shared decision-making and repeated measurement of symptoms and functioning.

For less severe depression, NICE favours low-intensity and less intrusive approaches first, including guided self-help, behavioural activation, structured exercise and psychological therapy; antidepressants are not routinely first-line unless they are the person's informed preference. For more severe depression, psychological therapy, antidepressant medication, or a combination may all be appropriate first-line options, chosen collaboratively. Combination treatment is especially important when severity, persistence or functional impairment is substantial.

When initial treatment fails, the task is broader than simply changing tablets. Clinicians should revisit diagnosis, bipolarity, substance use, adherence, dose and duration, sleep, physical illness, neurodevelopmental conditions, trauma, psychosocial adversity and the quality or fit of psychotherapy. Further-line strategies include switching antidepressants, combining medication and psychotherapy, specialist augmentation with lithium or some second-generation antipsychotics, and physical treatments such as repetitive transcranial magnetic stimulation (rTMS) or electroconvulsive therapy (ECT).

Rapid-acting glutamatergic treatments have changed the research landscape. Esketamine has regulatory approval in several countries, including US monotherapy approval for treatment-resistant depression in 2025, but NICE still does not recommend esketamine nasal spray for treatment-resistant depression in the NHS. Intravenous ketamine is used in some specialist settings but UK guidance remains cautious. Psychedelic-assisted therapies remain investigational rather than routine clinical practice.

The central 2026 message

Depression care is moving away from one-size-fits-all treatment toward personalised, measurement-based and mechanism-informed care. The science is increasingly sophisticated, but routine clinical practice should still distinguish robust evidence from promising biomarkers, commercial claims and research-stage interventions.

1. What depression is - and what it is not

Depression is a syndrome characterised by persistent low mood and/or loss of interest or pleasure, accompanied by changes in cognition, motivation, sleep, appetite, energy, psychomotor activity, self-evaluation and thoughts about death. The diagnosis depends not merely on the presence of symptoms, but on their persistence, clustering, severity, impact and context.

A depressive episode can be understood at several levels simultaneously: as a recognisable clinical syndrome; as a pattern of psychological processes such as withdrawal, rumination and negative self-appraisal; as a disturbance of brain and body systems involved in reward, salience, stress and regulation; and as an experience shaped by relationships, work, inequality, trauma, illness, loss and meaning. These accounts are complementary rather than mutually exclusive.

Depression is not the same as ordinary sadness

Sadness is a normal human emotion. Clinical depression is more pervasive and persistent, often includes loss of pleasure and motivation, and commonly impairs work, relationships, self-care or basic daily functioning. Some people do not describe feeling “sad” at all; they may report emptiness, irritability, exhaustion, numbness, cognitive slowing or inability to enjoy anything.

Symptom domain	Typical examples	Clinical significance
Mood and reward	Low mood, emptiness, reduced pleasure, emotional blunting	Anhedonia may be particularly disabling and can persist even after mood begins to improve.
Cognition	Poor concentration, indecision, slowed thinking, hopelessness, guilt	Can mimic or worsen ADHD-like executive difficulties and impair work or study.
Body and sleep	Insomnia or hypersomnia, fatigue, appetite/weight change, pain	Physical symptoms may dominate the presentation, especially in primary care.
Behaviour and motivation	Withdrawal, reduced activity, self-neglect, loss of routine	Avoidance can become a maintaining cycle and is a key target for behavioural activation.
Psychomotor	Agitation or slowing	Marked change can indicate greater severity and may influence urgency of treatment.
Risk	Thoughts of death, self-harm or suicide; severe self-neglect	Requires direct, proportionate risk assessment and a safety plan; urgent care may be required.

2. Symptoms, severity and functional impact

Modern practice increasingly avoids treating severity as a score alone. Symptom questionnaires such as the PHQ-9 are useful for screening and monitoring, but clinical severity also depends on functional impairment, duration, recurrence, psychotic or melancholic features, physical compromise, suicidality, comorbidity, social support and the person’s ability to care for themselves.

NICE now uses the broad terms “less severe” and “more severe” depression rather than relying only on older mild/moderate/severe labels. This reflects the reality that treatment choice should be matched to the individual rather than mechanically determined by a single threshold.

Measurement-based care

Repeated symptom measures are most useful when paired with functional goals: returning to work, attending college, parenting, reconnecting socially, sleeping normally, exercising, managing finances or regaining enjoyment. A falling questionnaire score without meaningful functional recovery is not full remission.

3. Current models: beyond the serotonin story

The monoamine hypothesis helped drive antidepressant development, but the idea that depression is simply caused by “low serotonin” is too narrow. Contemporary research emphasises interacting systems and recognises substantial heterogeneity: two people with the same diagnosis may have different dominant mechanisms and treatment needs.

Model / process	What current thinking suggests	Clinical status in 2026
Neural networks and reward	Altered functioning in reward, salience, threat and cognitive-control networks may contribute to anhedonia, negative bias and impaired regulation.	Strong research framework; not yet used as a routine diagnostic scan.
Stress and HPA-axis regulation	Chronic stress can alter cortisol signalling, sleep, immunity and neural plasticity. Early adversity can increase later vulnerability.	Clinically relevant concept; no single cortisol test diagnoses depression.
Neuroplasticity	Effective treatments may converge on changes in synaptic function, learning and network flexibility rather than simply changing transmitter levels.	Important modern model; supports interest in rapid-acting and experience-dependent treatments.
Inflammation / immunometabolism	A subgroup shows low-grade inflammatory and metabolic abnormalities, often with fatigue, hypersomnia, increased appetite or obesity.	Promising subtype research; routine anti-inflammatory prescribing or biomarker-based selection is not established.
Circadian and sleep disruption	Sleep timing, insomnia, hypersomnia and circadian misalignment can both contribute to and result from depression.	Directly clinically actionable: assess sleep disorders, routines, light exposure and medication timing.
Psychological learning and cognition	Rumination, avoidance, self-criticism, negative prediction and reduced rewarding activity can maintain depression.	Direct treatment targets in CBT, behavioural activation, mindfulness and related therapies.
Social and environmental factors	Loneliness, poverty, discrimination, insecure work/housing, caring burdens, relationship conflict and trauma can initiate or perpetuate symptoms.	Core to formulation; treatment that ignores ongoing adversity may underperform.

Precision psychiatry aims to identify clinically meaningful subgroups or “biotypes” that predict treatment response using combinations of symptoms, genetics, inflammatory markers, digital data, neuroimaging or machine learning. The direction is scientifically important, but current evidence does not justify routine brain scans, inflammatory panels or pharmacogenomic testing as a universal way to select an antidepressant.

4. Assessment and differential diagnosis

A high-quality assessment establishes the depressive syndrome while actively looking for alternative or coexisting explanations. This matters because an apparently “treatment-resistant” depression may actually be bipolar depression, substance-related mood change, an untreated sleep disorder, a physical illness, trauma-related disorder, ADHD with burnout and demoralisation, or a combination of these.

· Clarify onset, duration, recurrence, triggers, diurnal variation, anhedonia, cognition, sleep, appetite, energy, psychomotor change and functional impairment.

· Ask directly about thoughts of death, self-harm, suicide, intent, planning, access to means, protective factors, recent losses and changes in risk.

· Screen for past periods of elevated or unusually irritable mood, reduced need for sleep, increased activity, impulsivity or other features suggesting bipolarity.

· Assess alcohol, cannabis, stimulants, opioids, sedatives and other substance use, including withdrawal and medication-related effects.

· Consider physical contributors such as thyroid disease, anaemia, vitamin deficiency where clinically indicated, neurological illness, chronic pain, endocrine disorders, infection, medication adverse effects and sleep apnoea.

· Assess anxiety, PTSD, OCD, eating disorders, psychosis, neurodevelopmental conditions and personality-related difficulties where relevant.

· Understand relationships, work, finances, housing, caring responsibilities, discrimination, isolation, trauma and current safeguarding issues.

· Review previous treatments carefully: dose, duration, adherence, benefit, adverse effects, withdrawal, quality of psychotherapy and reasons treatment stopped.

Clue	Consider	Why it matters
Reduced need for sleep + episodic activation	Bipolar spectrum disorder	Antidepressant-only strategies may be ineffective or destabilising in some patients.
Loud snoring, witnessed apnoeas, morning headache, daytime sleepiness	Obstructive sleep apnoea	Can produce fatigue, low mood and cognitive symptoms and requires specific treatment.
Restlessness, distractibility, longstanding executive dysfunction from childhood	ADHD or other neurodevelopmental condition	Depression may be secondary to chronic impairment, burnout or repeated failure experiences.
Marked anxiety, hypervigilance, nightmares, trauma reminders	PTSD / trauma-related disorder	Trauma-focused treatment may be central.
Heavy alcohol/cannabis/stimulant use or withdrawal	Substance-related mood symptoms	Treatment must address the substance pattern and associated risks.
Psychotic guilt, nihilistic beliefs, hallucinations	Psychotic depression	Requires specialist treatment; antidepressant + antipsychotic and/or ECT may be considered.

5. Treatment principles and shared decision-making

Treatment is best framed as a sequence of collaborative experiments informed by evidence, preference and previous response. The person should understand likely benefits, delays before benefit, adverse effects, withdrawal effects, alternatives and the plan if the first choice does not work.

Clinical situation	Common evidence-based approach	Important nuance
Less severe depression	Active monitoring, guided self-help, behavioural activation, CBT-based interventions, structured exercise, other psychological options.	NICE does not routinely recommend an antidepressant first-line unless it is the person’s informed preference.
More severe depression	Individual CBT plus an antidepressant is a high-ranking option; antidepressant or psychological therapy alone may also be chosen.	Severity, previous response, waiting time, patient preference and functional impairment matter.
Partial response	Optimise treatment, address adherence and maintaining factors; add psychotherapy or medication depending on what has already been tried.	Do not confuse a small symptom reduction with remission.
Non-response	Reassess diagnosis and adequacy; switch treatment or use a different modality.	Repeated similar trials without reformulation can prolong illness.
Severe / life-threatening depression	Urgent specialist assessment; consider ECT when a rapid response is needed.	Examples include severe self-neglect, not eating/drinking or very high suicide risk.

6. Psychological treatments

Psychotherapy is not a generic category. Different approaches target different maintaining processes, and the therapeutic relationship, treatment fidelity, dose and active engagement all affect outcomes. NHS Talking Therapies in England provides NICE-recommended interventions through self-referral or professional referral, delivered in person or remotely.

Therapy	Main target / method	Where it may fit
Cognitive behavioural therapy (CBT)	Links thoughts, emotions and behaviour; tests unhelpful beliefs and develops alternative responses.	Broad evidence base across less and more severe depression.
Behavioural activation (BA)	Systematically reverses withdrawal and avoidance by increasing meaningful and rewarding activity.	Especially useful where inactivity, loss of routine and reduced reinforcement are prominent.
Interpersonal therapy (IPT)	Focuses on grief, role transitions, conflict and interpersonal patterns.	Useful where relationship or life-role changes are central.
Counselling for depression / person-centred experiential approaches	Uses a therapeutic relationship to process emotional experience and strengthen self-understanding.	NICE-recognised option within NHS Talking Therapies.
Mindfulness-based cognitive therapy (MBCT)	Develops decentring from thoughts and awareness of relapse patterns.	Particularly relevant to relapse prevention in recurrent depression.
Behavioural couples therapy	Works directly with relationship patterns that may maintain depression.	When relationship distress contributes to the episode or partner involvement may help.
Dynamic interpersonal therapy (DIT)	Brief psychodynamic approach focusing on recurring relational patterns.	Available in NHS Talking Therapies for selected presentations.

Therapy should be active, not merely supportive

Evidence-based depression therapies usually involve formulation, goals, structured learning and change between sessions. Support and validation matter, but therapy is most effective when it also changes the processes maintaining depression.

7. Antidepressant medication

Antidepressants are effective for many people with moderate or severe depression, but response is variable and no single drug is best for everyone. Choice should be personalised around previous response, anxiety, sleep, pain, sexual side effects, weight, cardiovascular risk, overdose toxicity, interactions, pregnancy considerations and withdrawal risk.

Class / examples	Potential advantages	Common limitations / cautions
SSRIs: sertraline, fluoxetine, citalopram, escitalopram	Often first choices because of familiarity, broad evidence and relative safety in overdose.	GI effects, sexual dysfunction, activation or sedation, hyponatraemia, bleeding risk; withdrawal differs by drug.
SNRIs: venlafaxine, duloxetine	Useful where depression coexists with anxiety; duloxetine may help some pain syndromes.	BP effects, sweating, sexual effects; venlafaxine can have prominent withdrawal and is more toxic in overdose than many SSRIs.
Mirtazapine	Can help insomnia, anxiety and poor appetite; lower rate of sexual dysfunction than many serotonergic drugs.	Sedation, increased appetite and weight gain.
Vortioxetine	Multimodal serotonergic drug; may be considered where cognitive symptoms or sexual tolerability influence choice.	Nausea; cost/formulary restrictions may apply.
TCAs	Effective antidepressants; some have additional pain indications.	Anticholinergic and cardiovascular effects; dangerous in overdose, so risk assessment is essential.
MAOIs / specialist options	Can be effective in difficult-to-treat depression and selected phenotypes.	Important food/drug interactions and switching requirements; usually specialist-led.

A first review should occur early enough to assess tolerability, adherence and risk, with closer follow-up for younger adults or where suicide risk is a concern. Improvement often begins within the first few weeks, but an adequate treatment trial usually requires sufficient dose and duration. If medication works, continuation for months after remission reduces relapse risk; people with recurrent or high-risk depression may benefit from longer maintenance treatment.

Withdrawal is not the same as addiction

Stopping antidepressants can cause physical and psychological withdrawal symptoms, particularly after long-term use or with shorter half-life drugs. Tapering should usually be gradual and individualised. Withdrawal does not mean that antidepressants produce craving or compulsive drug-seeking in the way addictive substances do.

Lifestyle interventions should not be presented as “just exercise” or as evidence that depression is a failure of willpower. They are treatments and recovery supports that can modify sleep, inflammation, reward exposure, self-efficacy, social contact and physical health. They are usually best integrated with psychological or pharmacological care when depression is more severe.

A large 2024 network meta-analysis of 218 randomised trials found clinically meaningful reductions in depressive symptoms with exercise, with walking/jogging, yoga and strength training among the better-supported modalities. However, confidence in many comparisons was low because of study limitations. The practical message is to prescribe activity collaboratively and progressively, not to demand intense exercise from someone who is profoundly fatigued or medically unwell.

Domain	Practical focus	Why it matters
Exercise	Start at an achievable level; use walking, resistance work, classes, sport or other preferred activity.	Can directly reduce symptoms and improves cardiovascular, metabolic and sleep health.
Sleep and circadian rhythm	Consistent wake time, daylight exposure, treat insomnia and screen for sleep apnoea/restless legs.	Sleep disturbance strongly interacts with mood, cognition and relapse risk.
Alcohol and drugs	Assess patterns without moralising; reduce harmful use and treat dependence where present.	Alcohol, cannabis and other substances can worsen mood, sleep, motivation and treatment response.
Nutrition	Regular balanced meals; address deficiency or metabolic disease where clinically indicated.	Supports general health; avoid unsupported “antidepressant diet” claims.
Social connection	Rebuild meaningful contact, community roles and activities gradually.	Isolation both results from and maintains depression.
Work, money and housing	Address debt, employment, benefits, occupational stress and insecure housing.	Social adversity can be an active driver of symptoms; medical treatment alone may be insufficient.

9. Further-line and treatment-resistant depression

Treatment-resistant depression (TRD) is commonly defined as failure to respond adequately to at least two standard treatments, but the label should trigger diagnostic and therapeutic review rather than imply that the person is intrinsically “resistant”. Some experts increasingly use the term difficult-to-treat depression to emphasise modifiable contributors and long-term management.

Before declaring treatment resistance

Confirm diagnosis; exclude bipolarity and substance-related mood change; check dose, duration and adherence; review physical illness, sleep and drug interactions; ask whether psychotherapy was evidence-based and delivered adequately; identify ongoing trauma or social adversity; and establish what outcomes actually improved.

· Optimise or switch antidepressant medication when the first choice has not produced sufficient benefit.

· Add a psychological treatment if medication alone has not achieved remission, or add medication where psychotherapy alone has been insufficient.

· In specialist care, consider antidepressant combinations or augmentation with lithium or selected second-generation antipsychotics, balancing additional benefit against metabolic, neurological and other adverse effects.

· Consider ECT for severe depression when a rapid response is required, where other treatments have failed, or where the person has previously responded and prefers it.

· Consider rTMS in appropriate specialist services; it is non-invasive and does not require a general anaesthetic.

· Use longer-term relapse prevention and rehabilitation goals rather than cycling indefinitely through acute treatments without a coherent plan.

10. ECT, rTMS, ketamine and esketamine

Treatment	What it is	Current place in practice
ECT	A controlled electrical stimulus under general anaesthesia producing a therapeutic seizure.	Among the most effective treatments for severe depressive illness; NICE recommends considering it when rapid response is needed, other treatments have failed, or the patient prefers it based on prior benefit. Cognitive adverse effects require careful consent and monitoring.
rTMS	Repeated magnetic stimulation of targeted cortical regions, usually over multiple outpatient sessions.	NICE considers the safety evidence adequate and supports use with normal governance arrangements. Useful particularly when medication has failed or is poorly tolerated.
IV ketamine	Sub-anaesthetic ketamine infusion producing rapid antidepressant effects in some patients.	Used in some specialist services; effects can be rapid but durability, repeated dosing, dissociation, cardiovascular effects, misuse risk and service standards require careful management. NICE 2026 surveillance did not lead to new routine recommendations.
Esketamine nasal spray	The S-enantiomer of ketamine administered under clinical supervision.	Approved in the US for treatment-resistant depression, including as monotherapy from 2025. In the UK, NICE still does not recommend it for TRD because of cost-effectiveness/evidence considerations.

ECT remains particularly important because severe depression can be medically and psychiatrically life-threatening. It should not be caricatured as a historical “last resort”; modern ECT is delivered with anaesthesia, muscle relaxation, formal consent processes and cognitive monitoring. At the same time, memory effects can be significant for some people and must be discussed honestly.

11. Psychedelics and other emerging approaches

Interest in psilocybin and other psychedelic-assisted interventions has accelerated because early trials have shown potentially large and rapid effects in selected patients. The therapeutic model usually combines a drug session with preparation, psychological support and subsequent integration rather than treating the psychedelic as a conventional take-home antidepressant.

However, enthusiasm should not outrun evidence. The Royal College of Psychiatrists’ 2025 position emphasised that promising findings do not yet provide enough high-quality evidence for routine clinical use and highlighted the need for careful patient selection, monitoring and research governance. Most classical psychedelics remain controlled drugs in the UK and are not routine treatments for depression.

Promising is not the same as proven

Key unresolved issues include durability of benefit, expectancy and blinding effects in trials, optimal psychotherapy model, safety in people with bipolar or psychotic vulnerability, interactions with other medication, and how intensive treatment could be delivered safely and equitably at scale.

Other developing areas include accelerated forms of TMS, digital therapeutics, passive digital phenotyping, AI-supported treatment prediction, pharmacogenomics, anti-inflammatory strategies for selected subgroups and novel neuroplasticity-targeting drugs. None currently replaces careful clinical assessment and shared decision-making.

12. Special clinical situations

Situation	Clinical priority
Psychotic depression	Specialist mental health care. NICE recommends considering antidepressant plus antipsychotic treatment; ECT may be appropriate, particularly when rapid response is needed.
Bipolar depression suspected	Clarify history before escalating antidepressants. Refer or seek specialist advice where bipolarity is plausible.
Pregnancy / postpartum period	Balance risks of untreated illness with treatment risks; use perinatal expertise for complex or severe illness.
Older adults	Review physical illness, cognition, polypharmacy, falls, sodium, cardiovascular risk and social isolation; do not undertreat solely because of age.
Depression with chronic pain or physical illness	Use integrated treatment and consider how pain, disability, sleep, inflammation and medication interact.
Neurodevelopmental conditions	Adapt communication and therapy where necessary; distinguish longstanding executive or sensory/social difficulties from the depressive episode.
Substance misuse	Treat both conditions in an integrated way; intoxication, withdrawal and ongoing use can alter mood, sleep and risk.

13. Relapse prevention and recovery

Recovery is more than symptom reduction. A person may no longer meet diagnostic criteria yet still have residual fatigue, sleep disturbance, cognitive impairment, social withdrawal or loss of confidence. Residual symptoms predict relapse, so treatment should continue until functioning and resilience have meaningfully recovered where possible.

· Identify each person’s early warning signs: altered sleep, withdrawal, rumination, loss of routine, irritability, reduced self-care or substance use.

· Create a written relapse plan covering who to contact, what to restart, what to stop, and how family or trusted people can help.

· Continue effective antidepressant treatment for an appropriate maintenance period and taper gradually when stopping.

· Use CBT or MBCT relapse-prevention strategies for people with recurrent depression or persistent vulnerabilities.

· Protect sleep, exercise, structure, relationships and meaningful roles as active components of recovery.

· Review physical health: depression is associated with poorer cardiovascular and metabolic outcomes, and some treatments also require physical monitoring.

14. What good depression care looks like in 2026

It takes the symptoms seriously without reducing the person to a diagnosis.
It assesses suicide risk directly and repeatedly, while avoiding the false reassurance of a single risk score.
It looks for bipolarity, substance use, trauma, sleep disorders, physical illness and neurodevelopmental conditions before calling treatment ineffective.
It offers genuine choices between evidence-based psychological, pharmacological, physical and behavioural treatments.
It measures both symptoms and real-world functioning.
It treats withdrawal effects as real and plans antidepressant discontinuation carefully.
It uses specialist augmentation or physical treatments when indicated rather than repeating low-yield medication trials indefinitely.
It remains open to new science - inflammation, precision psychiatry, ketamine, psychedelics and neurostimulation - while being clear about what is established, what is off-label and what remains experimental.
It addresses loneliness, work, debt, housing, relationships and other social drivers rather than pretending depression exists only inside the brain.
It aims for recovery, agency and relapse prevention, not merely a lower questionnaire score.

When urgent assessment is needed

Urgent clinical assessment is appropriate when there is imminent suicide risk, severe self-neglect, inability to maintain hydration or nutrition, psychotic depression, rapidly worsening agitation, suspected mania/mixed state, severe withdrawal/intoxication, or a serious safeguarding concern. In an emergency, use local emergency or crisis services.

References and further reading

NICE. Depression in adults: treatment and management (NG222). Last reviewed January 2026; minor updates through December 2025. Link
NICE. Recommendations: Depression in adults - NG222. Link
NICE. January 2026 exceptional surveillance of NG222. Link
NICE. Repetitive transcranial magnetic stimulation for depression (HealthTech guidance / former IPG542). Link
NHS. Treatment - Depression in adults. Link
NHS England. NHS Talking Therapies for anxiety and depression. Link
Royal College of Psychiatrists. Antidepressants. Published March 2025. Link
Royal College of Psychiatrists. Depression. Link
Royal College of Psychiatrists. More research needed into psychedelics as potential treatments for mental disorders. 19 September 2025. Link
Marx W, Penninx BWJH, Solmi M, et al. Major depressive disorder. Nature Reviews Disease Primers. 2023;9:44. Link
Cui L, Li S, Wang S, et al. Major depressive disorder: hypothesis, mechanism, prevention and treatment. Signal Transduction and Targeted Therapy. 2024;9:30. Link
Hannon K, et al. Parsing Clinical and Neurobiological Sources of Heterogeneity in Depression. Biological Psychiatry. 2025. Link
Penninx BWJH, et al. Immuno-metabolic depression: from concept to implementation. 2024/2025. Link
Singh MK, Thase ME. Current progress in targeted pharmacotherapy to treat symptoms of major depressive disorder: moving from broad-spectrum treatments to precision psychiatry. CNS Spectrums. 2025. Link
Noetel M, et al. Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2024;384:e075847. Link
US FDA. Spravato (esketamine) - 2025 supplemental approval for treatment-resistant depression as monotherapy. Link
World Health Organization. Depressive disorder (depression). Link

About this guide

This article is an educational overview for adults and reflects UK clinical guidance alongside international research available to August 2026. It does not replace an individual assessment, diagnosis or treatment plan. Medication and physical treatments require appropriate clinical prescribing, monitoring and informed consent. Recommendations can change as new evidence and regulatory decisions emerge.

Depression