What is depression and why is its treatment crucial?

Depression (Latin: depressio – lowering) is one of the most common mental disorders worldwide, affecting over 280 million people of all ages and backgrounds, according to estimates by the World Health Organization (WHO). It is a complex condition with biological, psychological, and social underpinnings that significantly reduces quality of life, work capacity, and daily functioning, and in severe cases may lead to suicidal thoughts and attempts.

In Poland, the number of antidepressant medications sold in 2023 exceeded 30 million packages – one-third more than five years earlier (PEX PharmaSequence data). This is a concerning indicator of the growing scale of the problem, but also evidence of increasing public awareness and a greater willingness to seek help.

Effective treatment of depression is possible. Modern psychiatry and psychology offer a wide range of therapeutic methods grounded in solid scientific evidence. However, the key to success lies in a comprehensive and individualized approach that takes into account the biological mechanisms of the disorder, treatment history, physical health status, psychosocial context, and the patient’s own preferences.

This article provides a comprehensive guide to depression treatment methods – from standard pharmacotherapy and psychotherapy, through modern neuromodulation techniques, to emerging and breakthrough therapies such as ketamine and psilocybin. It is intended for both patients and their families, as well as professionals, including psychologists, psychiatrists, and primary care physicians.

Diagnosis as a prerequisite for effective treatment of depression

It is essential to rule out organic causes of depressive symptoms, including thyroid disorders (hypothyroidism), deficiencies in vitamin D, B12, and iron, as well as neurological conditions. Diagnosis is made by a psychiatrist, although a psychologist and a primary care physician may also be involved in the diagnostic process.

An accurate diagnosis is the foundation of any effective depression treatment. Depression is not a single, uniform condition – it includes mild, moderate, and severe depressive episodes (with or without psychotic features), recurrent depressive disorder, dysthymia (chronic low mood), postpartum depression, as well as depression associated with somatic illnesses or other mental disorders.

Diagnosis is based on clinical criteria, most commonly in accordance with ICD-11 (International Classification of Diseases, 11th revision) or DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition). A diagnosis requires the presence of characteristic symptoms for at least two weeks, such as depressed mood, anhedonia (loss of the ability to experience pleasure), or reduced energy, accompanied by other psychological and somatic symptoms.

Pharmacotherapy in the treatment of depression

Pharmacotherapy plays a key role in the treatment of moderate and severe depression. Antidepressants target the neurobiological disturbances underlying the disorder – primarily dysregulation of neurotransmitter systems (serotonergic, noradrenergic, dopaminergic), dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis, and neuroplastic changes in brain structures responsible for emotional regulation and stress response [Malhi et al., 2018, The Lancet].

Classes of antidepressants

SSRIs – selective serotonin reuptake inhibitors

SSRIs are the first-line treatment for depression due to their favorable safety profile and good tolerability. This group includes fluoxetine, sertraline, escitalopram, paroxetine, and citalopram. They work by inhibiting the reuptake of serotonin in the synapse, thereby increasing its availability. The therapeutic effect typically appears after 2–4 weeks of use.

A meta-analysis by Cipriani et al. (2018, The Lancet), which included 522 clinical trials with over 116,000 patients, demonstrated that all studied antidepressants were more effective than placebo, with differences primarily related to side effect profiles and tolerability [Cipriani et al., 2018].

SNRIs – serotonin and norepinephrine reuptake inhibitors

Wenlafaksyna, duloksetyna i milnacipran działają na dwa układy neuroprzekaźnikowe jednocześnie. Wykazują szczególną skuteczność w depresji z komponentem bólowym, lękowym oraz u pacjentów z towarzyszącymi chorobami somatycznymi. Są często wybierane, gdy SSRI nie przynoszą satysfakcjonującej odpowiedzi.

Venlafaxine, duloxetine, and milnacipran act on two neurotransmitter systems simultaneously. They are particularly effective in depression with a pain component, anxiety symptoms, and in patients with comorbid somatic conditions. They are often chosen when SSRIs do not produce a satisfactory response.

TCAs – tricyclic antidepressants

Medications in this group (amitriptyline, clomipramine, imipramine) are among the oldest antidepressants and demonstrate high efficacy. However, due to numerous side effects (cardiotoxicity, sedation, anticholinergic effects), they are currently considered second- or third-line treatments. They are used, among others, in depression with a strong pain or anxiety component.

Multimodal and other antidepressants

Mirtazapine, vortioxetine, trazodone, and agomelatine are examples of medications with different mechanisms of action, which may be particularly useful in cases of non-response to SSRI/SNRI treatment or in specific symptom profiles (e.g., sleep disturbances, co-occurring anxiety). Vortioxetine is especially notable for its beneficial effects on cognitive function in patients with depression.

Principles of pharmacotherapy

Effective pharmacotherapy for depression requires adherence to several key clinical principles:

• The choice of medication should be individualized, taking into account the clinical presentation, age, sex, comorbidities, concurrent medications, and patient preferences.
• The therapeutic effect is delayed, usually appearing after 2–4 weeks. Patients should be informed of this to prevent premature discontinuation.
• After achieving remission, treatment should be continued for at least 6–12 months to prevent relapse (continuation phase).
• Abrupt discontinuation may lead to withdrawal symptoms (especially with SSRIs and SNRIs); therefore, medication should be tapered gradually under medical supervision.
• If there is no response to the first medication (after 4–6 weeks at an adequate dose), the psychiatrist may consider switching the drug, augmentation, or another treatment strategy.

Psychotherapy in the treatment of depression

Psychotherapy is one of the most extensively studied and most effective methods for treating depression – both as a standalone intervention (in mild and moderate cases) and in combination with pharmacotherapy (in severe depression). The combination of these approaches leads to better and more sustained outcomes than either method used alone [Cuijpers et al., 2020, World Psychiatry].

Cognitive Behavioral Therapy (CBT)

Cognitive Behavioral Therapy is the most well-documented psychotherapeutic method for treating depression and is recommended, among others, by the UK’s National Institute for Health and Care Excellence (NICE) as a first-line treatment. CBT is based on the assumption that our thoughts, emotions, and behaviors are closely interconnected, and that changing negative patterns of thinking can alter how we feel and act.

In depression treatment, CBT focuses on identifying and modifying automatic negative thoughts (Beck’s cognitive triad: negative views of the self, the world, and the future), behavioral activation (gradual re-engagement in activities), problem-solving, and developing coping strategies for stress.

Research shows that patients who complete CBT have a twofold lower risk of depression relapse compared to those treated with pharmacotherapy alone [Cuijpers et al., 2020]. A systematic review of meta-analyses published in 2024 (Kowalski et al., Polish Association for Cognitive and Behavioral Therapy) confirms the high effectiveness of CBT across a wide range of depression severity levels.

CBT typically consists of 12 to 20 sessions and can be delivered individually, in groups, or online (iCBT). Studies indicate that online CBT platforms demonstrate comparable effectiveness to in-person therapy in cases of mild to moderate depression.

Interpersonal Therapy (IPT)

Interpersonal therapy focuses on the relationship between the quality of interpersonal relationships and depressive symptoms. It addresses four main problem areas: grief following loss, interpersonal conflicts, life transitions (such as retirement or job loss), and interpersonal deficits (social isolation). IPT is particularly effective for patients whose depression is linked to stressful life events or relationship difficulties.

Psychodynamic therapy

Psychodynamic therapy (including short-term psychodynamic therapy) is based on the premise that depression stems from unresolved internal conflicts, difficult past experiences, and relational patterns formed during childhood. Meta-analytic studies confirm its effectiveness in treating depression, although results are typically achieved more gradually than with CBT.

Mindfulness-Based Cognitive Therapy (MBCT)

Mindfulness-Based Cognitive Therapy combines elements of CBT with mindfulness practices. It is particularly recommended as a method for preventing depression relapse – studies show that in patients with a history of three or more depressive episodes, MBCT reduces the risk of relapse by approximately 43% compared to standard treatment (Kuyken et al., 2016, JAMA Psychiatry).

Other therapeutic approaches

Other approaches used in the treatment of depression include systemic therapy (which considers the family context), Gestalt therapy, schema therapy (particularly useful in chronic depressive patterns linked to early experiences), and psychodrama. The choice of approach should be tailored to the patient’s needs, preferences, and personality.

Treatment-resistant depression – modern treatment methods

Treatment-resistant depression (TRD) is defined as a lack of adequate response to at least two different antidepressants administered at appropriate doses and for a sufficient duration (at least 4–6 weeks) during the current depressive episode. It is estimated that TRD affects approximately 25–30% of patients seeking psychiatric care [Prof. Piotr Gałecki, National Consultant in Psychiatry, 2025].

Advanced pharmacological and biological treatment methods are used in TRD, as outlined below.

Electroconvulsive therapy (ECT)

Electroconvulsive therapy (ECT) is one of the longest-used and most effective biological treatments for treatment-resistant depression. Contrary to common misconceptions shaped by popular culture (e.g., the film One Flew Over the Cuckoo’s Nest), modern ECT is a safe, painless procedure (performed under general anesthesia with muscle relaxants) and highly effective.

The effectiveness of ECT in severe treatment-resistant depression is estimated at 70–90%. Dr. Anna Antosik-Wójcińska from the Institute of Psychiatry and Neurology notes that improvement may be visible after the first sessions. The treatment typically consists of 8–15 sessions, performed 2–3 times per week.

The exact mechanism of action of ECT is not fully understood, but it is associated with modulation of neurotransmitter systems (serotonergic, dopaminergic, noradrenergic), improved cerebral blood flow, and stimulation of neuroplasticity. Side effects mainly include transient short-term memory disturbances, headaches, and muscle pain, which usually resolve within 24 hours.

ECT is particularly indicated in patients with severe depression accompanied by suicidal risk, catatonia, during pregnancy (when pharmacotherapy is contraindicated), in older adults, and in situations where rapid improvement is essential. Professor Piotr Gałecki emphasizes that “electroconvulsive therapy is an exceptionally effective and safe treatment method – it can be used in pregnant women and elderly patients, which is rarely the case with other treatments” (interview, 2024).

In Poland, access to ECT remains limited compared to Western Europe and Scandinavia. In 2024, only 585 patients were treated across several academic and hospital centers.

Transcranial magnetic stimulation (TMS)

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that involves generating localized magnetic fields to induce electrical currents in specific areas of the cerebral cortex—most commonly the left dorsolateral prefrontal cortex (DLPFC), which shows reduced activity in depression.

TMS is an outpatient procedure, does not require anesthesia, and is generally well tolerated. A standard protocol includes approximately 20–30 sessions (five sessions per week over 4–6 weeks). While the effectiveness of TMS in treatment-resistant depression is somewhat lower than that of ECT, it has a more favorable side effect profile and is becoming increasingly accessible.

Modern TMS protocols, such as theta-burst stimulation (TBS), allow the duration of a session to be reduced from around 40 minutes to just 3 minutes while maintaining comparable therapeutic effectiveness.

Ketamine and esketamine – a breakthrough in the treatment of resistant depression

Ketamine, originally used as an anesthetic, has become one of the most significant innovations in psychiatry in recent years. It is a non-competitive NMDA receptor (glutamate) antagonist, which leads to rapid restoration of neuroplasticity and alleviation of depressive symptoms—often within hours of administration. This represents a fundamental difference compared to conventional antidepressants, which may take weeks to produce an effect.

Esketamine (Spravato)—the S-enantiomer of ketamine—has been approved in the form of a nasal spray for the treatment of treatment-resistant depression as well as depression with suicidal ideation or behavior. In Poland, since September 2023, a dedicated drug program (B.147) has been funding esketamine therapy in outpatient settings.

A meta-analysis by Nikolin et al. (EClinicalMedicine, 2023) confirms the effectiveness of ketamine in major depressive disorder. A clinical trial published in the New England Journal of Medicine (Anand et al., 2023) demonstrated comparable efficacy between ketamine and ECT in treatment-resistant depression without psychotic features. Professor Gałecki estimates that esketamine is effective in approximately 50% of patients with treatment-resistant depression.

Intravenous ketamine is used off-label in specialized centers, typically in a regimen of six infusions over two weeks, with the option of maintenance therapy. Esketamine is administered intranasally twice a week for four weeks, then once weekly, and eventually once every two weeks.

Side effects of ketamine and esketamine include transient dissociative symptoms, increased blood pressure, nausea, and dizziness. Due to their addictive and psychotomimetic potential, treatment must be conducted under strict medical supervision. Ceban et al. (2021) emphasize the need for careful monitoring of adverse effects, especially during long-term use.

Deep brain stimulation (DBS) and vagus nerve stimulation (VNS)

Deep brain stimulation (DBS) and vagus nerve stimulation (VNS) are invasive methods used in the most severe cases of treatment-resistant depression, when other treatments have failed. DBS involves the implantation of electrodes into specific brain regions (including Brodmann area 25), while VNS involves stimulating the vagus nerve באמצעות an implanted device. Both methods remain under intensive clinical investigation and are available only in highly specialized centers.

Psychedelic-assisted therapy – the future of depression treatment?

In recent years, psychedelic substances—primarily psilocybin (the active compound in hallucinogenic mushrooms)—have attracted significant scientific interest as potential therapeutic tools in the treatment of depression, particularly treatment-resistant depression, as well as depression associated with terminal illness.

Psilocybin is a 5-HT2A serotonin receptor agonist and operates through a mechanism distinct from ketamine. It induces functional reorganization of brain networks, including reduced activity in the default mode network (DMN), whose hyperactivity is associated with rumination and negative thought patterns characteristic of depression.

A randomized controlled trial by Carhart-Harris et al. (published, among others, in the New England Journal of Medicine, 2021) showed that a 25 mg dose of psilocybin administered with psychological support produced comparable or superior therapeutic outcomes compared to escitalopram (an SSRI) in patients with moderate to severe depression. Vollenweider and Preller (Nature Reviews Neuroscience, 2020) describe the neurobiological mechanisms of psychedelics and their therapeutic potential.

In Poland, the National Science Centre has allocated 2 million PLN for research into the medical use of psilocybin, including its application in treating depression and alcohol dependence. Australia and some U.S. states have already allowed the clinical use of psilocybin and MDMA under controlled conditions.

Researchers emphasize the need for caution. Horowitz and Moncrieff (2021) point to gaps in the evidence regarding esketamine, while van Elk and Fried (2023) warn against repeating the mistakes of 20th-century psychopharmacology. Dr. Agnieszka Wsół from the Medical University of Warsaw has highlighted the potential cardiotoxic risks of psychedelic substances even at low doses. Psychedelic-assisted therapy remains experimental and requires further investigation in large, multicenter clinical trials.

Stress as a factor sustaining depression

One of the key mechanisms contributing both to the development and recurrence of depression is chronic psychological and biological stress. Hans Selye, a pioneer in stress research, described it as a general adaptation syndrome which, under prolonged overload, leads to the “exhaustion” of the body’s biological and psychological resources.

Contemporary research confirms that chronic stress leads to dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, excessive cortisol production, and neuroplastic changes in the hippocampus—a structure crucial for memory and emotional regulation. McEwen (1998, Annals of the New York Academy of Sciences) described the concept of allostatic load as the cumulative biological cost of adapting to chronic stress.

Schneiderman et al. (2005, Psychological Bulletin) estimate that a significant proportion of visits to primary care physicians involve conditions in which stress plays an important etiological role. Chronic stress is associated with cardiovascular diseases, sleep disturbances, weakened immunity, muscle pain, and digestive disorders.

Reducing stress is therefore an important component of depression treatment and relapse prevention. Effective strategies include psychotherapy (particularly CBT and MBCT), relaxation techniques (such as Schultz’s autogenic training and Jacobson’s progressive muscle relaxation), physical exercise, as well as changes in the living and working environment.

Lifestyle and nutrition in depression treatment

Physical activity

Regular physical activity is one of the best-documented non-pharmacological methods supporting depression treatment. Schuch et al. (2018, American Journal of Psychiatry) published a meta-analysis indicating that physically active individuals have a significantly lower risk of developing depression compared to those with a sedentary lifestyle.

The mechanisms through which exercise alleviates depression include increased neurogenesis in the hippocampus (via elevated levels of BDNF—brain-derived neurotrophic factor), normalization of the HPA axis, improved sleep quality, increased levels of endorphins and monoamines, and a positive impact on self-esteem and sense of agency.

Recommendations typically include moderate aerobic activity (such as brisk walking, cycling, or swimming) for at least 30 minutes per day, 3–5 times per week. It has been shown that in patients with mild to moderate depression, regular exercise can be as effective as pharmacotherapy.

Diet and the gut microbiome

An increasing body of evidence points to the significant role of diet in mental health. Meta-analyses suggest that a Mediterranean-style diet (rich in vegetables, fruits, whole grains, fish, and olive oil) is associated with a lower risk of depression compared to a Western diet (high in processed foods, saturated fats, and sugar).

Grosso et al. (2014, Nutrients) demonstrated in a meta-analysis that omega-3 fatty acids (EPA and DHA), found primarily in fatty marine fish, may have a moderate antidepressant effect as an adjunct to standard depression treatment.

A particularly active area of research is the gut–brain axis and the role of the gut microbiome in mood regulation. Disruptions in gut microbiota composition (dysbiosis) have been linked to chronic inflammation, which may play a role in the pathogenesis of depression. Probiotics and prebiotic diets (rich in fiber and fermented foods) are increasingly being studied as potential complementary approaches in depression treatment.

Deficiencies in micronutrients—particularly vitamin D, B vitamins (B6, B9/folate, B12), magnesium, and zinc—may exacerbate depressive symptoms. Supplementation should be preceded by laboratory testing and discussed with a physician.

Sleep and circadian rhythm

Sleep disturbances are among the most common symptoms of depression, but they also play a significant role in maintaining the disorder. Maintaining good sleep hygiene—regular bedtimes and wake times, limiting exposure to blue light before sleep, avoiding daytime naps, and establishing a calm evening routine—is an important component of depression management.

Cognitive Behavioral Therapy for Insomnia (CBT-I) is recommended as the first-line treatment for chronic insomnia, including cases co-occurring with depression.

Social support and the role of family in depression treatment

Social support—particularly from family and close relationships—is a crucial prognostic factor in depression. Santini et al. (2015, Journal of Affective Disorders) demonstrated that low levels of social support and feelings of isolation significantly worsen outcomes and increase the risk of relapse, whereas stable interpersonal relationships promote recovery and enhance treatment effectiveness.

The family of a person experiencing depression plays a key role in encouraging treatment initiation and adherence. It is essential to understand that depression is a medical condition, not a sign of weakness or lack of willpower. Criticism, trivializing symptoms, or applying pressure (“just pull yourself together”) may deepen the patient’s sense of guilt and helplessness.

Particularly important is the response of close relatives to warning signs that may indicate suicidal thoughts. In such situations, immediate contact with a psychiatrist or referral to a psychiatric emergency department is necessary. If there is a direct threat to life, emergency services should be contacted (112) or the person should be taken to the nearest emergency unit.

For caregivers and family members, maintaining their own mental health is equally important. Seeking support—whether through family support groups or mental health professionals—can help them cope more effectively with the demands of caregiving.

Depression treatment as a process – phases and stages

Depression treatment progresses through several phases, the understanding of which is important for both patients and their families:

1. Acute phase (symptom reduction)

The goal of the acute phase is to achieve a therapeutic response (a reduction of symptoms by at least 50%) and remission (minimal or no symptoms). This phase typically lasts 6–12 weeks. During this time, the patient remains under close psychiatric supervision, and the treatment plan may be adjusted depending on the response.

2. Continuation phase (relapse prevention)

After remission is achieved, treatment should continue for at least 6–12 months (in the case of a first episode) or two years or longer (in recurrent depression) to prevent relapse. Premature discontinuation of medication is one of the most common causes of relapse.

3. Maintenance phase (prevention of future episodes)

In patients with recurrent depression (at least three episodes) or in cases where episodes are severe and significantly impair functioning, long-term preventive treatment is recommended—both pharmacological and psychotherapeutic (e.g., MBCT). Studies indicate that properly conducted maintenance therapy can prevent 22–38% of subsequent depressive episodes.

Depression treatment in selected patient groups

Depression during pregnancy and postpartum

Postpartum depression affects 10–15% of mothers after childbirth and requires specialized care. Treatment must consider the safety of both mother and child, particularly during breastfeeding. Sertraline and nortriptyline are considered relatively safe during lactation. Psychotherapy (CBT, IPT) may be the first-line treatment in milder cases. ECT is one of the few treatment options that can be used during pregnancy.

Depression in older adults

Depression in older individuals is often underdiagnosed and undertreated, as its symptoms may be mistaken for the “natural” aging process. Treatment requires particular caution in pharmacotherapy due to pharmacokinetic changes, polypharmacy, and comorbid conditions. ECT has demonstrated high effectiveness and safety in this population.

Depression in children and adolescents

Depression in children and adolescents may present differently than in adults—more often through irritability, oppositional behavior, somatic complaints, or academic difficulties. Psychotherapy (age-adapted CBT) is the first-line treatment. Pharmacotherapy (fluoxetine is the only SSRI approved for use in children in Poland) is considered when psychotherapy is insufficient or in more severe cases, always with careful monitoring.

Where to seek help? First steps in depression treatment

If depression is suspected in oneself or a loved one, the first step is to consult a physician—either a primary care doctor or a psychiatrist. The clinician will conduct an initial assessment, evaluate symptom severity (e.g., using standardized scales such as PHQ-9 or BDI-II), and propose a further treatment plan.

In Poland, psychiatric care is available through the public healthcare system (mental health clinics, Community Mental Health Centers) as well as privately. Psychotherapy is provided by psychologists and psychotherapists—it is important to choose a specialist with documented training from an accredited psychotherapy school (e.g., certified by recognized professional associations).

In crisis situations involving suicidal thoughts, immediate contact should be made with:

• A psychiatric emergency service or hospital emergency department
• A helpline for adults in emotional crisis: 116 123 (free, available 24/7)
• A helpline for children and adolescents: 116 111
• Emergency number: 112

Summary: effective depression treatment requires a comprehensive approach

Depression is a serious condition, but in the majority of cases it is treatable. Modern psychiatry and psychology offer a broad range of therapeutic options—from pharmacotherapy and psychotherapy, through neuromodulation techniques (TMS, ECT), to emerging treatments such as ketamine/esketamine and, potentially in the future, psilocybin.

The key elements of effective treatment include:

• Early diagnosis and initiation of treatment
• Individualized selection of therapeutic methods
• Combining pharmacotherapy with psychotherapy (especially in moderate and severe cases)
• Support from family and social environment
• Lifestyle changes (physical activity, diet, sleep hygiene)
• Patience and adherence to treatment recommendations
• Long-term continuation and preventive treatment

Although motivation and active participation of the patient are important, this should not be interpreted as responsibility for the course of the illness. Depression is a medical condition that requires the same level of care and attention as any other chronic disease. Access to reliable, evidence-based treatment is a fundamental right of every patient.

References and scientific sources

The article is intended for informational and educational purposes only. It does not replace consultation with a physician or a mental health professional. If you suspect depression, consult a qualified mental health specialist.

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