Lithium and the anticonvulsants carbamazepine, lamotrigine, and valproic acid are used as mood stabilizers to treat bipolar disorder. These mood stabilizers are used for long-term mood stabilization but have not demonstrated the ability to quickly treat acute bipolar depression. Lithium is preferred for long-term mood stabilization. Carbamazepine effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or a more schizoaffective clinical picture. It is less effective in preventing relapse than lithium or valproate. Since then, valproate has become a commonly prescribed treatment, and is effective in treating manic episodes. Lamotrigine has some efficacy in treating bipolar depression, and this benefit is greatest in more severe depression. It has also been shown to have some benefit in preventing bipolar disorder relapses, though there are concerns about the studies done, and is of no benefit in rapid cycling subtype of bipolar disorder. The effectiveness of topiramate is unknown.

Antipsychotic medications are effective for short-term treatment of bipolar manic episodes and appear to be superior to lithium and anticonvulsants for this purpose. Atypical antipsychotics are also indicated for bipolar depression refractory to treatment with mood stabilizers. Olanzapine is effective in preventing relapses, although the supporting evidence is weaker than the evidence for lithium.

The most common treatment for reducing bipolar II disorder symptoms is medication, usually in the form of mood stabilizers. However, treatment with mood stabilizers may produce a flat affect in the patient, which is dose-dependent. Concurrent use of SSRI antidepressants may help some with bipolar II disorder, though these medications should be used with caution because it is believed that they may cause a hypomanic switch.

The pharmaceutical management of bipolar II disorder is not generally supported by strong evidence, with limited randomised controlled trials (RCTs) published in the literature. Some medications used are:

- Lithium - There is strong evidence that lithium is effective in treating both the depressive and hypomanic symptoms in bipolar II. In addition, its action as a mood stabilizer can be used to decrease the risk of hypomanic switch in patients treated with antidepressants.

- Anticonvulsants - there is evidence that lamotrigine decreases the risk of relapse in rapid cycling bipolar II. It appears to be more effective in bipolar II than bipolar I, suggesting that lamotrigine is more effective for the treatment of depressive rather than manic episodes. Doses ranging from 100–200 mg have been reported to have the most efficacy, while experimental doses of 400 mg have rendered little response. A large, multicentre trial comparing carbamazepine and lithium over two and a half years found that carbamazepine was superior in terms of preventing future episodes of bipolar II, although lithium was superior in individuals with bipolar I. There is also some evidence for the use of valproate and topiramate, although the results for the use of gabapentin have been disappointing.

- Antidepressants - there is evidence to support the use of SSRI and SNRI antidepressants in bipolar II. Indeed, some sources consider them to be one of the first line treatments. However, antidepressants also pose significant risks, including a switch to mania, rapid cycling, and dysphoria and so many psychiatrists advise against their use for bipolar. When used, antidepressants are typically combined with a mood stabilizer.

- Antipsychotics - there is good evidence for the use of quetiapine, and it has been approved by the FDA for this indication. There is also some evidence for the use of risperidone, although the relevant trial was not placebo controlled and was complicated by the use of other medications in some of the patients.

- Dopamine agonists - there is evidence for the efficacy of pramipexole from one RCT.

The first line of pharmacotherapy is usually SSRIs due to their more tolerable nature and reduced side effects compared to the irreversible monoamine oxidase inhibitors or tricyclic antidepressants. Studies have found that the mean response to antidepressant medications for people with dysthymia is 55%, compared with a 31% response rate to a placebo. The most commonly prescribed antidepressants/SSRIs for dysthymia are escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine. It often takes an average of 6–8 weeks before the patient begins to feel these medications' therapeutic effects. Additionally, STAR*D, a multi-clinic governmental study, found that people with overall depression will generally need to try different brands of medication before finding one that works specifically for them. Research shows that 1 in 4 of those who switch medications get better results regardless of whether the second medication is an SSRI or some other type of antidepressant.

In a meta-analytic study from 2005, it was found that SSRIs and TCAs are equally effective in treating dysthymia. They also found that MAOIs have a slight advantage over the use of other medication in treating this disorder. However, the author of this study cautions that MAOIs should not necessarily be the first line of defense in the treatment of dysthymia, as they are often less tolerable than their counterparts, such as SSRIs.

Tentative evidence supports the use of amisulpride to treat dysthymia but with increased side effects.

A combination of antidepressant medication and psychotherapy has consistently been shown to be the most effective line of treatment for people diagnosed with dysthymia. Working with a psychotherapist to address the causes and effects of the disorder, in addition to taking antidepressants to help eliminate the symptoms, can be extremely beneficial. This combination is often the preferred method of treatment for those who have dysthymia. Looking at various studies involving treatment for dysthymia, 75% of people responded positively to a combination of cognitive behavioral therapy (CBT) and pharmacotherapy, whereas only 48% of people responded positively to just CBT or medication alone.

In a meta-analytic study from 2008, researchers found an effect size of -0.07 (Cohen's d) between pharmacologic treatments and psychological treatments for depressive disorders, suggesting pharmacologic treatments to be slightly more effective, though the results were not found to be statistically significant. This small effect is true only for SSRIs, with TCAs and other pharmacologic treatments showing no differences from psychological treatments. Additionally, there have been several studies yielding results that indicate that severe depression responds more favorably to psychotherapy than pharmacotherapy.

The use of lithium and quetiapine (Seroquel) have both shown to be particularly valuable, though several other medications of the anticonvulsants and atypical antipsychotics classes may also be helpful.

- Lithium – Lithium has been shown to help stabilize the mood of patients suffering from cyclothymia and as well as bipolar disorders. It also aids in the prevention of acute suicidal and manic episodes. Dosage must be carefully monitored as lithium has a plethora of side effects.

- Atypical antipsychotics – (e.g., quetiapine (Seroquel), also olanzapine (Zyprexa), and risperidone (Risperdal).

- Anticonvulsants – (e.g., valproic acid, lamotrigine (Lamictal), and valproate semisodium (Depakote)).

- Electroconvulsive therapy – Through a systematic review done by Versiani, Cheriaux, and Landeira-Fernandez, it was determined that the efficacy and safety of ECT in patients with bipolar disorder had been poorly investigated and the evidence had methodological limitations.

There are few studies specifically testing psychotherapy for cyclothymia. The following is a list of some common types of therapy. They have different amounts of support for use with bipolar disorder and other mood disorders. If a treatment helps with bipolar disorder, it is a reasonable choice for use with cyclothymia until better evidence becomes available.

- Cognitive behavioural therapy (CBT) – Has been found to reduce depression.

- Dialectical behavioral therapy (DBT)

- Interpersonal psychotherapy (IT)

- Interpersonal and social rhythm therapy (IPSRT)

- Group therapy

- Integrative therapy

- Person-centered therapy (PCT)

- Psychodynamic therapy

Treatment typically includes three things: the treatment of acute hypomania, the treatment of acute depression, and the prevention of the relapse of either hypomania or depression. The main goal is to make sure that patients do not harm themselves.

Several treatment guidelines recommend either the combination of a second-generation antidepressant and atypical antipsychotic or tricyclic antidepressant monotherapy or electroconvulsive therapy (ECT) as the first-line treatment for unipolar psychotic depression.

Pharmaceutical treatments can include tricyclic antidepressants, atypical antipsychotics, or a combination of an antidepressant from the newer, more well tolerated SSRI or SNRI categories and an atypical antipsychotic. Olanzapine may be an effective monotherapy in psychotic depression, although there is evidence that it is ineffective for depressive symptoms as a monotherapy; and olanzapine/fluoxetine is more effective. Quetiapine monotherapy may be particularly helpful in psychotic depression since it has both antidepressant and antipsychotic effects and a reasonable tolerability profile compared to other atypical antipsychotics. The current drug-based treatments of psychotic depression are reasonably effective but can cause side effects, such as nausea, headaches, dizziness, and weight gain. Tricyclic antidepressants are particularly dangerous in overdose due to their potential to cause potentially-fatal cardiac arrhythmias.

In the context of psychotic depression, the following are the most well-studied antidepressant/antipsychotic combinations

"First-generation"

- Amitriptyline/perphenazine

- Amitriptyline/haloperidol

"Second-generation"

- Venlafaxine/quetiapine?

- Olanzapine/fluoxetine

- Olanzapine/sertraline

In modern practice of ECT a therapeutic clonic seizure is induced by electric current via electrodes placed on an anaesthetised, unconscious patient. Despite much research the exact mechanism of action of ECT is still not known. ECT carries the risk of temporary cognitive deficits (e.g., confusion, memory problems), in addition to the burden of repeated exposures to general anesthesia.

Medications that have been shown to be effective in cases of treatment-resistant depression include lithium, triiodothyronine, benzodiazepines, atypical antipsychotics, and stimulants. Adding lithium may be effective for patients taking some types of antidepressants, I it does not appear to be effective in patients taking SSRI’s. Triiodothyroxine (T3) is a type of thyroid hormone and has been associated with improvement in mood and depression symptoms. Benzodiazepines may improve treatment-resistant depression by decreasing the adverse side effects caused by some antidepressants and therefore increasing patient compliance. Since the entry of olanzapine into psychopharmacology, many psychiatrists have been adding low dose olanzapine to antidepressants and other atypical antipsychotics such as aripiprazole and quetiapine.

Particularly, the combination of olanzapine and fluoxetine seems to be effective.

These have shown promise in treating refractory depression but come with serious side effects. Stimulants such as amphetamines and methylphenidate have also been tested with positive results but have a high potential for abuse. However, stimulants have been shown to be effective for the unyielding depressed combined lacking addictive personality traits or heart problems.

Ketamine has been tested as a rapid-acting antidepressant for treatment-resistant depression in bipolar disorder, and major depressive disorder.

Treatments for classic (winter-based) seasonal affective disorder include light therapy, medication, ionized-air administration, cognitive-behavioral therapy and carefully timed supplementation of the hormone melatonin.

Photoperiod-related alterations of the duration of melatonin secretion may affect the seasonal mood cycles of SAD. This suggests that light therapy may be an effective treatment for SAD. Light therapy uses a lightbox which emits far more lumens than a customary incandescent lamp. Bright white "full spectrum" light at 10,000 lux, blue light at a wavelength of 480 nm at 2,500 lux or green (actually cyan or blue-green) light at a wavelength of 500 nm at 350 lux are used, with the first-mentioned historically preferred.

Bright light therapy is effective with the patient sitting a prescribed distance, commonly 30–60 cm, in front of the box with her/his eyes open but not staring at the light source for 30–60 minutes. A study published in May 2010 suggests that the blue light often used for SAD treatment should perhaps be replaced by green or white illumination. Discovering the best schedule is essential. One study has shown that up to 69% of patients find lightbox treatment inconvenient and as many as 19% stop use because of this.

Dawn simulation has also proven to be effective; in some studies, there is an 83% better response when compared to other bright light therapy. When compared in a study to negative air ionization, bright light was shown to be 57% effective vs. dawn simulation 50%. Patients using light therapy can experience improvement during the first week, but increased results are evident when continued throughout several weeks. Most studies have found it effective without use year round but rather as a seasonal treatment lasting for several weeks until frequent light exposure is naturally obtained.

Light therapy can also consist of exposure to sunlight, either by spending more time outside or using a computer-controlled heliostat to reflect sunlight into the windows of a home or office. Although light therapy is the leading treatment for seasonal affective disorder, prolonged direct sunlight or artificial lights that don't block the ultraviolet range should be avoided due to the threat of skin cancer.

SSRI (selective serotonin reuptake inhibitor) antidepressants have proven effective in treating SAD. Effective antidepressants are fluoxetine, sertraline, or paroxetine. Both fluoxetine and light therapy are 67% effective in treating SAD according to direct head-to-head trials conducted during the 2006 Can-SAD study. Subjects using the light therapy protocol showed earlier clinical improvement, generally within one week of beginning the clinical treatment. Bupropion extended-release has been shown to prevent SAD for one in eight people, but has not been compared directly to other preventive options in trials.

Negative air ionization, which involves releasing charged particles into the sleep environment, has been found effective with a 47.9% improvement if the negative ions are in sufficient density (quantity).

Depending upon the patient, one treatment (e.g., lightbox) may be used in conjunction with another (e.g., medication).

Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression.

Another explanation is that vitamin D levels are too low when people do not get enough Ultraviolet-B on their skin. An alternative to using bright lights is to take vitamin D supplements. However, studies did not show a link between vitamin D levels and depressive symptoms in elderly Chinese nor among elderly British women.

Physical exercise has shown to be an effective form of depression therapy, particularly when in addition to another form of treatment for SAD. One particular study noted marked effectiveness for treatment of depressive symptoms when combining regular exercise with bright light therapy. Patients exposed to exercise which had been added to their treatments in 20 minutes intervals on the aerobic bike during the day along with the same amount of time underneath the UV light were seen to make quick recovery.

Studies have shown a wide variability in the effectiveness of switching antidepressants, with anywhere from 25-70% of patients responding to a different antidepressant. There is support for the effectiveness of switching patients to a different SSRI; 50% of patients that were nonresponsive after taking one SSRI were responsive after taking a second type. Switching patients to a different class of antidepressants may also be effective. Patients who are nonresponsive after taking an SSRI may respond to bupropion or a MAOI.

There are different types of treatments available for mood disorders, such as therapy and medications. Behaviour therapy, cognitive behaviour therapy and interpersonal therapy have all shown to be potentially beneficial in depression. Major depressive disorder medications usually include antidepressants, while bipolar disorder medications can consist of antipsychotics, mood stabilizers, anticonvulsants and/or lithium. Lithium specifically has been proven to reduce suicide and all causes of mortality in people with mood disorders. If mitochondrial dysfunction or mitochondrial diseases are the cause of mood disorders like bipolar disorder, then it has been hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options.

There is some evidence that omega-3 fatty acids fish oil supplements containing high levels of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) are effective in the treatment of, but not the prevention of major depression. However, a Cochrane review determined there was insufficient high quality evidence to suggest Omega-3 fatty acids were effective in depression. There is limited evidence that vitamin D supplementation is of value in alleviating the symptoms of depression in individuals who are vitamin D deficient. There is some preliminary evidence that COX-2 inhibitors have a beneficial effect on major depression. Lithium appears effective at lowering the risk of suicide in those with bipolar disorder and unipolar depression to nearly the same levels as the general population. There is a narrow range of effective and safe dosages of lithium thus close monitoring may be needed. Low-dose thyroid hormone may be added to existing antidepressants to treat persistent depression symptoms in people who have tried multiple courses of medication. Limited evidence suggests stimulants such as amphetamine and modafinil may be effective in the short term, or as add on therapy.

Efforts are made to find a treatment which targets the proposed specific underlying pathophysiology of psychotic depression. A promising candidate was mifepristone, which by competitively blocking certain neuro-receptors, renders cortisol less able to directly act on the brain and was thought to therefore correct an overactive HPA axis. However, a Phase III clinical trial, which investigated the use of mifepristone in PMD, was terminated early due to lack of efficacy.

Transcranial magnetic stimulation (TMS) is being investigated as an alternative to ECT in the treatment of depression. TMS involves the administration of a focused electromagnetic field to the cortex to stimulate specific nerve pathways.

Research has shown that psychotic depression differs from non-psychotic depression in a number of ways: potential precipitating factors, underlying biology, symptomatology beyond psychotic symptoms, long-term prognosis, and responsiveness to psychopharmacological treatment and ECT.

Treatment of mixed states is typically based upon administration of mood stabilizing medication, which may include anticonvulsants such as valproic acid; atypical antipsychotics such as olanzapine, aripiprazole, and ziprasidone; or first-generation antipsychotics such as haloperidol. There is question of lithium's efficacy for treatment of mixed states due to conflicting conclusions drawn from various trials and research. Mood stabilizers work to reduce the manic symptoms associated with the mixed state, but they are not considered particularly effective for improving concurrent depressive symptoms.

Involutional melancholia is classically treated with antidepressants and mood elevators.

Electroconvulsive therapy may also be used. Mid-century, there was a consensus that the technique indeed 'yields the best results in the long-lasting depressions of the change of life, the so-called "involutional melancholias", which before this form of treatment was introduced often required years of hospitalization'. The 21st century also records 'an excellent and rapid clinical response found in melancholia of recent onset...in older rather than younger patients' with ECT

Treatment is effective in about 80% of identified cases, when treatment is provided. Effective management requires a biopsychosocial approach, combining pharmacotherapy and psychotherapy. Therapy generally results in improved quality of life, enhanced functional capacity, possible improvement in medical health status, increased longevity, and lower health care costs. Improvement should be evident as early as two weeks after the start of therapy, but full therapeutic effects may require several months of treatment. Psychotherapy and medication are the two primary treatment approaches.Therapy for older patients should be continued for longer periods than are typically used in younger patients.

Electroconvulsive therapy (ECT) is a standard psychiatric treatment in which seizures are electrically induced in patients to provide relief from psychiatric illnesses. ECT is used with informed consent as a last line of intervention for major depressive disorder.

A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or bipolar. Follow-up treatment is still poorly studied, but about half of people who respond relapse within twelve months.

Aside from effects in the brain, the general physical risks of ECT are similar to those of brief general anesthesia. Immediately following treatment, the most common adverse effects are confusion and memory loss. ECT is considered one of the least harmful treatment options available for severely depressed pregnant women.

A usual course of ECT involves multiple administrations, typically given two or three times per week until the patient is no longer suffering symptoms. ECT is administered under anesthetic with a muscle relaxant. Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some patients receive maintenance ECT.

ECT appears to work in the short term via an anticonvulsant effect mostly in the frontal lobes, and longer term via neurotrophic effects primarily in the medial temporal lobe.

Pharmacotherapy for acute episodes of depression usually is effective and free of complications. Underuse or misuse of antidepressants and prescribing inadequate dosages are the most common mistakes physicians make when treating elderly patients for depression. Only 10 to 40 percent of depressed elderly patients are given medication. Antidepressants, in general, may also work by playing a neuroprotective role in how they relieve anxiety and depression. It's thought that antidepressants may increase the effects of brain receptors that help nerve cells keep sensitivity to glutamate which is an organic compound of a nonessential amino acid. This increased support of nerve cells lowers glutamate sensitivity, providing protection against the glutamate overwhelming and exciting key brain areas related to depression. Antidepressant medications are often the first treatment choice for adults with moderate or severe depression, sometimes along with psychotherapy. Although antidepressants may not cure depression, they can lead to remission, which is the disappearance or nearly complete reduction of depression symptoms.

Treatment of minor depressive disorder has not been studied as extensively as major depressive disorder. Although there are often similarities in the treatments used, there are also differences in what may work better for the treatment of minor depressive disorder. Some third-party payers do not pay to cover treatment for minor depressive disorder.

The leading treatment techniques for minor depressive disorder are the use of antidepressants and therapy. Typically, patients with minor depression were treated by watchful waiting, prescribed antidepressants, and given brief supportive counseling, but Problem-Solving Treatment for Primary Care (PST-PC) is a Cognitive-Behavioral Therapy that has gained popularity. In one study, Problem-Solving Treatment for Primary Care (PST-PC) and Paroxetine, an antidepressant, were shown to be equally effective in significantly reducing symptoms. In another study, PST-PC was compared with the more typical care of the time and shown to reduce symptoms more quickly. Although the use of antidepressants has been widely used, not all agree that it is an appropriate treatment for some minor depression disorder settings.

Another alternative that has been researched is the use of St. John's wort ("Hypericum perforatum"). This herbal treatment has been studied by various groups with various results. Some studies show evidence of the treatment being helpful to treat minor depression, but others show that it does no better than the placebo.

Cognitive behavioral therapy (CBT) is a newer therapy than exposure therapy, available for those unable or unwilling to undergo exposure therapy. Cognitive therapy has been shown to be useful in reducing intrusive thoughts, but developing a conceptualization of the obsessions and compulsions with the patient is important.

For a number of years, scholars debated amongst themselves whether or not antipsychotic drugs had a tendency to increase depression or simply help the patient manage their mental illness. However, conclusive evidence points to antipsychotic drugs actually helping patients with their depression while simultaneously assisting in the suppression of schizophrenic episodes. Specifically risperidone, olanzapine, quetiapine, fluphenazine, haloperidol, and L-sulpiride have done the best in drug trials pertaining to people with schizophrenia. Along with antipsychotic drugs, post-schizophrenic patients may receive antidepressants to actively treat the depression. Drugs are certainly not the only answer, though. At the base of both depression and schizophrenia, social withdrawal is a shared symptom between the two. People suffering from schizophrenia require a strong support system to be healthy, just as is the case with the rest the human population. The opportunity to become a working citizen is another way to ward off depression in patients with schizophrenia, helping them create social ties and a feeling of accomplishment.

Individuals suffering from endogenous depression require treatment plans that focus on the internal, cognitive thought processes since internal stressors are the root of somatic symptoms. Individual cognitive therapy (ICT) is therefore a common treatment used to gain insight to the individual's internal conflicts or thoughts that are motivating their distressing symptoms. Once the cause of the symptoms are identified, sessions are used to develop new coping skills, behavior modification, and changes in beliefs.

As preventative measures, pharmaceuticals such as SSRI's and antidepressants may also be utilized to avoid further development or progression to Major Depressive Disorder. There have been few treatments targeted specifically toward Endogenous Depression; therefore, symptoms are often managed similarly to Major Depressive Disorder. One such treatment is electroconvulsive therapy (ECT). ECT is used as a treatment option for endogenous depression in adults, however, practitioners avoid the use of ECT in young adolescents due to rates of injury.

Antidepressants or antipsychotic medications may be used for more severe cases if intrusive thoughts do not respond to cognitive behavioral or exposure therapy alone. Whether the cause of intrusive thoughts is OCD, depression, or post-traumatic stress disorder, the selective serotonin reuptake inhibitor (SSRI) drugs (a class of antidepressants) are the most commonly prescribed. Intrusive thoughts may occur in persons with Tourette syndrome (TS) who also have OCD; the obsessions in TS-related OCD are thought to respond to SSRI drugs as well.

Antidepressants which have been shown to be effective in treating OCD include fluvoxamine (trade name Luvox), fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and clomipramine (Anafranil). Although SSRIs are known to be effective for OCD in general, there have been fewer studies on their effectiveness for intrusive thoughts. A retrospective chart review of patients with sexual symptoms treated with SSRIs showed the greatest improvement was in those with intrusive sexual obsessions typical of OCD. A study of ten patients with religious or blasphemous obsessions found that most patients responded to treatment with fluoxetine or clomipramine. Women with postpartum depression often have anxiety as well, and may need lower starting doses of SSRIs; they may not respond fully to the medication, and may benefit from adding cognitive behavioral or response prevention therapy.

Patients with intense intrusive thoughts that do not respond to SSRIs or other antidepressants may be prescribed typical and atypical neuroleptics including risperidone (trade name Risperdal), ziprasidone (Geodon), haloperidol (Haldol), and pimozide (Orap).

Studies suggest that therapeutic doses of inositol may be useful in the treatment of obsessive thoughts.