Depression and mood disorders

Article written and reviewed by Dr Luca Moretti

In everyday language, the term depression is often used to indicate any condition of sadness, discouragement, or reduced emotional well-being. In medicine, however, it may refer to a single symptom, a depressive syndrome, a time-limited episode, or a specific psychiatric disorder. Diagnosis therefore does not depend on the presence of sad mood alone, but on the combination of symptoms, their duration, severity, impairment of personal, family, social, or occupational functioning, and the possible presence of clinical risks.
Depressive disorders include conditions characterized predominantly by depressed mood, loss of interest or pleasure, cognitive changes, somatic symptoms, and reduced functioning. Depressive episodes may also occur in bipolar disorders, in which they are associated over the course of life with manic or hypomanic episodes. Distinguishing unipolar depression from bipolar depression is essential because diagnostic formulation, prognosis, risk of recurrence, and treatment strategies differ.
This section provides a systematic pathway covering mood episodes, the main depressive and bipolar disorders, manifestations at different stages of life, pathogenic mechanisms, and treatment options. The pages are organized in a clinical progression: from fundamental concepts to individual diagnoses, followed by pharmacotherapy, psychotherapies, physical treatments, neuromodulation, and emerging approaches.

Mood episodes and fundamental concepts

To understand mood disorders correctly, it is necessary to distinguish an individual episode from the overall diagnosis. An episode describes a configuration of symptoms present for a defined period, whereas the disorder is defined by considering the entire clinical history, the sequence of episodes, their duration, possible recurrence, and exclusion of medical conditions, medications, or substances capable of producing similar manifestations.
A major depressive episode is characterized by persistent depressed mood or loss of interest and pleasure, associated with cognitive, neurovegetative, psychomotor, and somatic symptoms. A manic episode instead involves a marked and persistent alteration in mood, energy, and activity, with substantial functional impairment or need for hospitalization. Hypomania has similar features but lower intensity and functional consequences, while still representing a key diagnostic element for recognizing bipolar II disorder. Presentations in which symptoms of opposite polarity coexist are discussed in the page devoted to mixed episode and mixed features.

• Depression: overview
• Major depressive episode
• Manic episode
• Hypomanic episode
• Mixed episode and mixed features
• Summary table of mood episodes

Depressive disorders and bipolar disorders

The presence of a major depressive episode is not, by itself, sufficient to diagnose major depressive disorder. The entire course of illness must be reconstructed and any previous manic or hypomanic episodes identified. A previous manic episode points toward bipolar I disorder, whereas the combination of major depressive episodes and hypomanic episodes characterizes bipolar II disorder.
Major depressive disorder may present as a single episode or follow a recurrent course. Persistent depressive disorder, traditionally called dysthymia, is instead characterized by prolonged depressive symptoms, often less intense but capable of causing significant and lasting impairment. Cyclothymia is characterized by chronic alternation of hypomanic and depressive symptoms that do not fully meet, in intensity or duration, the requirements for the respective full episodes.
Unspecified categories are used when the presentation causes clinically significant distress or functional impairment but the available information or features do not allow more precise classification. Comparative pages provide an immediate overview of differences among the main disorders without replacing in-depth assessment of each diagnosis.

• Major depressive disorder
• Persistent depressive disorder or dysthymia
• Overview of bipolar disorders
• Bipolar I disorder
• Bipolar II disorder
• Cyclothymia
• Bipolar disorder not otherwise specified
• Depressive disorder not otherwise specified
• Summary table of depressive and bipolar disorders

Depression across the lifespan and biological foundations

Depression can occur at any stage of life, but its manifestations are influenced by age, level of neuropsychological development, individual ways of expressing distress, family and social context, and the presence of comorbid conditions. In childhood, depressed mood may manifest through irritability, loss of interest in play, school difficulties, somatic symptoms, withdrawal, or behavioral changes. In adolescence, isolation, declining performance, impulsivity, risk-taking behaviors, sleep disturbances, and the emergence of self-harm thoughts become particularly important.
In older adults, depression may present with somatic symptoms, psychomotor slowing, apathy, cognitive disturbances, loss of autonomy, and worsening of the consequences of physical illness. Diagnosis therefore requires careful differentiation from neurocognitive disorders, bereavement, medication adverse effects, and medical illnesses capable of producing depressive symptoms.
Pathogenesis cannot be reduced to a single neurochemical alteration. It involves genetic predisposition, regulation of monoaminergic systems, synaptic plasticity, neurotrophins, the hypothalamic-pituitary-adrenal axis, circadian rhythms, immune and inflammatory processes, brain reward circuits, and the interaction between individual vulnerability and environmental events.

• Childhood depression
• Adolescent depression
• Depression in older adults
• Biochemistry and pathogenesis of depression

Pharmacological treatment

The choice of pharmacological treatment depends on the diagnosis, episode severity, predominant symptoms, suicide risk, presence of psychotic or mixed features, comorbidities, previous treatments, drug interactions, and individual tolerability. Antidepressants are a fundamental component of therapy for many depressive disorders, but they are not all equivalent and should not be used indiscriminately in every mood disorder.
Tricyclic antidepressants and monoamine oxidase inhibitors retain specific clinical indications, while requiring particular attention to safety profile, interactions, and adverse effects. Second-generation antidepressants include classes that differ in mechanism of action, efficacy, tolerability, and possible preferential indications. Antipsychotics may be used in psychotic depression, augmentation strategies for treatment-resistant depression, mania, and different phases of bipolar disorder.
Lithium is a central treatment for stabilization of bipolar disorder and relapse prevention, but it may also be used as an augmentation strategy in selected forms of treatment-resistant depression. Pharmacological management requires clinical monitoring, assessment of response, surveillance for adverse effects, and particular caution during dose changes or treatment discontinuation.

• Treatment of depression: general principles
• Tricyclic antidepressants
• Monoamine oxidase inhibitors
• Second-generation antidepressants
• Antipsychotics or neuroleptics
• Lithium salts
• Summary table of pharmacotherapy

Psychotherapies and psychological interventions

Structured psychotherapies are among the fundamental tools for treating depression. They may be used alone in presentations appropriate for psychological intervention or integrated with pharmacotherapy in more severe cases, recurrent forms, and patients with relevant comorbidities or psychosocial factors. Selection depends on clinical characteristics, treatment goals, patient preferences, availability of qualified professionals, and evidence for the specific approach.
Cognitive behavioral therapy integrates cognitive and behavioral techniques to address dysfunctional thoughts, avoidance, and reduced rewarding activities. Cognitive therapy focuses mainly on interpretive schemas and dysfunctional beliefs, whereas behavioral therapy primarily targets behaviors that contribute to maintaining symptoms. Interpersonal therapy addresses the relationship among depressive symptoms, life events, and relational difficulties.
Other approaches target metacognitive processes, acceptance and psychological flexibility, structured problem solving, or conflicts and relational patterns. Mindfulness-Based Cognitive Therapy is used mainly for relapse prevention in selected patients. Music therapy, animal-assisted interventions, and reminiscence therapy may have a complementary role in specific settings, but they do not replace treatments of established efficacy when these are indicated.

• Psychological therapies for depression
• Cognitive behavioral therapy
• Behavioral therapy
• Cognitive therapy
• Interpersonal therapy
• Brief psychodynamic therapy
• Problem-solving therapy
• Metacognitive therapy
• Acceptance and commitment therapy
• Mindfulness-Based Cognitive Therapy
• Music therapy
• Pet therapy and animal-assisted interventions
• Reminiscence therapy
• Summary table of psychotherapies

Physical treatments and neuromodulation

Physical treatments and neuromodulation techniques include interventions that differ substantially in mechanism of action, efficacy, invasiveness, and indications. Electroconvulsive therapy is an established treatment for some forms of severe depression, particularly when psychotic symptoms, catatonia, high clinical risk, severe impairment of food intake, or a need for rapid response is present. It may also be considered when other treatments have not produced an adequate response.
Repetitive transcranial magnetic stimulation uses magnetic pulses to modulate the activity of specific cortical areas and is used mainly in depression that has not responded sufficiently to pharmacological treatments. Transcranial direct current stimulation applies low-intensity electrical currents through electrodes placed on the scalp, but its clinical role depends on the context and protocols used.
Vagus nerve stimulation requires implantation of a device and is reserved for selected situations of high treatment resistance. Deep brain stimulation is an invasive neurosurgical technique still limited to highly specialized and experimental settings. Selection of these interventions should follow a complete specialist assessment considering expected benefits, risks, alternatives, and individual patient characteristics.

• Electroconvulsive therapy
• Repetitive transcranial magnetic stimulation
• Transcranial direct current stimulation
• Vagus nerve stimulation
• Deep brain stimulation
• Summary table of neuromodulation therapies

Emerging approaches and personalized medicine

Therapeutic research is moving toward faster-acting interventions, new neurobiological targets, and strategies capable of improving treatment selection. Ketamine and esketamine act mainly by modulating glutamatergic neurotransmission and can produce a relatively rapid reduction in symptoms in selected patients with treatment-resistant depression. Their use requires defined protocols, clinical monitoring, and assessment of possible cardiovascular, dissociative, and neuropsychiatric effects.
Psychedelic substances are being studied in combination with structured psychological interventions, but they cannot be considered routine treatments outside authorized indications or research protocols. Nutraceuticals also have very different levels of evidence: some compounds have been evaluated as adjunctive strategies, whereas for others the available data are insufficient or heterogeneous.
Pharmacogenetics analyzes genetic variants that may primarily influence drug metabolism and tolerability. It can provide useful information in selected situations, but it is not currently able to identify with certainty the clinically most effective antidepressant for each individual patient. Treatment personalization therefore continues to depend on integrating clinical characteristics, medication history, comorbidities, patient preferences, and systematic monitoring of response.

• Nutraceuticals in depression
• Ketamine and esketamine
• Psychedelics in depression
• Pharmacogenetics in depression

Situations requiring urgent assessment

The emergence of suicidal thoughts, self-harm intent, planning of a suicidal act, inability to eat or meet basic needs, severe agitation, psychotic symptoms, catatonia, or rapid deterioration requires urgent medical assessment. A marked decrease in the need for sleep, abnormally increased energy, racing thoughts, impulsivity, disinhibition, or dangerous behavior may also indicate a manic or hypomanic episode and should be assessed promptly.
The information in this section is intended for scientific and educational purposes and does not replace individual clinical assessment. Diagnosis and treatment of mood disorders require a personalized pathway based on the complete clinical history, mental status examination, risk assessment, exclusion of possible organic or medication-related causes, and monitoring of the course over time.

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