Treatment of bipolar disorder

The use of psychotherapy to treat bipolar disorder has been found to reduce the relative risk of relapse at post-treatment (risk ratio=0.66) and follow-up time points (risk ratio=0.74). Although treatment for bipolar disorder was once centered around medications called mood stabilizers, which are used to prevent or control episodes of mania or depression, the United Nations Special Rapporteur in the right to health has said, Although the lifetime rate of suicide attempt in bipolar disorder is high (34%), guidelines for assessment of suicide risk are supported by evidence of "low" "overall strength". Although hospitalization was once a recommended practice, the United Nations' Committee on Rights of Persons with Disabilities recommends abolishing institutionalization and involuntary treatments "such as sedatives, mood stabilizers, electro-convulsive treatment, and conversion therapy". Legend: - negligible/very low/clinically insignificant effect + weak effect ++ moderate-level effect +++ strong effect Regulatory status of mood stabilisers == Mood stabilizers ==

Lithium salts Lithium salts have been used for centuries as a first-line treatment for bipolar disorder. In ancient times, doctors would send their mentally ill patients to drink from "alkali springs" as a treatment. Although they were not aware of it, they were actually prescribing lithium, which was present in high concentration within the waters. The therapeutic effect of lithium salts appears to be entirely due to the lithium ion, Li+. Its exact mechanism of action is uncertain, although there are several possibilities such as inhibition of inositol monophosphatase, modulation of G proteins or regulation of gene expression for growth factors and neuronal plasticity. Potential side effects from lithium include gastrointestinal upset, tremor, sedation, excessive thirst, frequent urination, cognitive problems, impaired motor coordination, hair loss, and acne. Lithium levels of 0.8-1.0 are effective for acute mania. For a faster onset of action, it is recommended to use an antipsychotic with evidence for treating mania. Lithium has also been proven in clinical trials to prevent suicide in people with bipolar disorder. In addition to its effects on suicide, lithium also decreases all-cause mortality in people with bipolar disorder. Anticonvulsants A number of anti-convulsant drugs are used as mood stabilizers, and the suspected mechanism is related to the theory that mania can "kindle" further mania, similar to the kindling model of seizures. Carbamazepine was the first anti-convulsant shown to be effective for treating bipolar mania. It has not been extensively studied in bipolar depression. Various other anti-convulsants have been tested in bipolar disorder, but there is little evidence of their effectiveness. Each anti-convulsant agent has a unique side-effect profile. Valproic acid can frequently cause sedation or gastrointestinal upset, which can be minimized by giving the related drug divalproex, which is available in an enteric-coated tablet. Second-generation or atypical antipsychotics (including aripiprazole, olanzapine, quetiapine, paliperidone, risperidone, and ziprasidone) have emerged as effective mood stabilizers. Antidepressant effectiveness varies, which may be related to different serotonergic and dopaminergic receptor binding profiles. A head-to-head randomized control trial in 2005 has also shown olanzapine monotherapy to be just as effective and safe as lithium in prophylaxis. The atypical antipsychotics differ somewhat in side effect profiles, but most have some risk of sedation, weight gain, and extrapyramidal symptoms (including tremor, stiffness, and restlessness). New treatments A variety of other agents have been tried in bipolar disorder, including benzodiazepines, calcium channel blockers, L-methylfolate, and thyroid hormone. In addition, riluzole, a glutamatergic drug used in ALS has been studied as an adjunct or monotherapy treatment in bipolar depression, with mixed and inconsistent results. The selective estrogen receptor modulator medication tamoxifen has shown rapid and robust efficacy treating acute mania in bipolar patients. This action is likely due not to tamoxifen's estrogen-modulating properties, but due to its secondary action as an inhibitor of protein Kinase C. Use of both typical and atypical antipsychotics is associated with risk of cognitive impairment, but the risk is higher for antipsychotics with more sedating effects. Among bipolar patients taking anticonvulsants, those on lamotrigine have a better cognitive profile than those on carbamazepine, valproate, topiramate, and zonisamide. Although decreased verbal memory and slowed psychomotor speed are common side effects of lithium use, these side effects usually disappear after discontinuation of lithium. Lithium may be protective of cognitive function in the long term since it promotes neurogenesis in the hippocampus and increases grey matter volume in the prefrontal cortex. == Antidepressants ==

Antidepressants are used with caution in bipolar disorder, as they may not be effective and may even induce mania. The concurrent use of an antidepressant and a mood stabilizer, instead of mood stabilizer monotherapy, may lower the risk of further bipolar depressive episodes in patients whose most recent depressive episode has been resolved. However, some studies have also found that antidepressants pose a risk of inducing hypomania or mania, sometimes in individuals with no prior history of mania. Saint John's Wort, a naturally occurring compound, is thought to function in a fashion similar to man-made antidepressants, and there are reports that suggest that it can also induce mania. For these reasons, some psychiatrists are hesitant to prescribe antidepressants for the treatment of bipolar disorder unless mood stabilizers have failed to have an effect, however, others feel that antidepressants still have an important role to play in treatment of bipolar disorder. Side effects vary greatly among different classes of antidepressants. Antidepressants are helpful in preventing suicides in people with bipolar disorder when they go in for the depressive phase. == NMDA-receptor antagonists ==

A single intravenous dose of ketamine may produce a rapid but transient antidepressant effect in bipolar depression, although the evidence is of low to very low certainty, and evidence for other glutamate receptor modulators or for sustained remission and safety remains inconclusive. == Dopamine agonists ==

In a single controlled study of twenty one patients, the dopamine D3 receptor agonist pramipexole was found to be highly effective in the treatment of bipolar depression. Treatment was initiated at 0.125 mg thrice daily and increased at a rate of 0.125 mg thrice daily to a limit of 4.5 mg per day until the patients' condition satisfactorily responded to the medication or they could not abide the side effects. The final average dosage was 1.7 mg ± 0.90 mg per day. The incidence of hypomania in the treatment group was no greater than in the control group. == Psychotherapy ==

Certain types of psychotherapy, used in combination with medication, may provide some benefit in the treatment of bipolar disorders. Psychoeducation has been shown to be effective in improving patients' compliance with their lithium treatment. Evidence of the efficacy of family therapy is not adequate to support unrestricted recommendation of its use. There is "fair support" for the utility of cognitive therapy. Evidence for the efficacy of other psychotherapies is absent or weak, often not being performed under randomized and controlled conditions. Well-designed Although medication and psychotherapy cannot cure the illness, therapy can often be valuable in helping to address the effects of disruptive manic or depressive episodes that have hurt a patient's career, relationships or self-esteem. Therapy is available not only from psychiatrists but from social workers, psychologists and other licensed counselors. == Jungian therapy ==

Jungian authors have likened the mania and depression of bipolar disorder to the Jungian archetypes 'puer' and 'senex'. The puer archetype is defined by the behaviors of spontaneity, impulsiveness, enthusiasm or mania and is symbolized by characters such as Peter Pan or the Greek god Hermes. In the case of the split puer-senex bipolarity the therapeutic task is to bring the puer and senex back into correlation by working with the patient's mental imagery." == Lifestyle changes ==

Sufficient sleep If sleeping is disturbed, the symptoms can occur. Sleep disruption may actually exacerbate the mental illness state. Those who do not get enough sleep at night, sleep late and wake up late, or go to sleep with some disturbance (e.g. music or charging devices) have a greater chance of having the symptoms and, in addition, depression. It is highly advised by psychiatric authorities to not sleep too late and to get enough high quality sleep. Self-management and self-awareness Understanding the symptoms, when they occur and ways to control them using appropriate medications and psychotherapy generally helps those diagnosed with bipolar disorder to lead a psychologically healthier life. Prodrome symptom detection has been shown to be used effectively to anticipate onset of manic episodes and requires close monitoring of bipolar symptoms. Because the offset of the symptoms is often gradual, even subtle mood changes and activity levels are monitored to help avoid a relapse. Maintaining a mood chart is a specific method used by patients and doctors to identify mood, environmental and activity triggers. Stress reduction Forms of stress may include having too much to do, too much complexity and conflicting demands among others. There are also stresses that come from the absence of elements such as human contact, a sense of achievement, constructive creative outlets, and occasions or circumstances that will naturally elicit positive emotions. Stress reduction will involve reducing things that cause anxiety and increasing those that generate happiness. It is not enough to just reduce the anxiety. Co-morbid substance use disorder Co-occurring substance misuse disorders, which are extremely common in bipolar patients, can cause a significant worsening of bipolar symptomatology and can cause the emergence of affective symptoms. The treatment options and recommendations for substance use disorders is wide but may include certain pharmacological and nonpharmacological treatment options. The role of cannabinoids Acute cannabis intoxication transiently produces perceptual distortions, psychotic symptoms and reduction in cognitive abilities in healthy persons and in severe mental disorder, and may impair the ability to safely operate a motor vehicle. Cannabis use is common in bipolar disorder; and is a risk factor for a more severe course of the disease by increasing frequency and duration of episodes. It is also reported to reduce age at onset. == Other treatments ==

Omega-3 fatty acids Omega-3 fatty acids may also be used as a treatment for bipolar disorder, particularly as a supplement to medication. An initial clinical trial by Stoll et al. produced positive results. However, since 1999, attempts to confirm this finding of beneficial effects of omega-3 fatty acids in several larger double-blind clinical trials have produced inconclusive results. It was hypothesized that the therapeutic ingredient in omega-3 fatty acid preparations is eicosapentaenoic acid (EPA) and that supplements should be high in this compound to be beneficial. A 2008 Cochrane systematic review found limited evidence to support the use of Omega-3 fatty acids to improve depression but not mania as an adjunct treatment for bipolar disorder. Omega-3 fatty acids may be found in fish, fish oils, algae, and to a lesser degree in other foods such as flaxseed, flaxseed oil and walnuts. Although the benefits of Omega-3 fatty acids remain debated, they are readily available at drugstores and supermarkets, relatively inexpensive, and have few known side effects. (All of these oils, however, have the capacity to exacerbate GERD—food sources may be a good alternative in such cases.) Exercise Exercise has also been shown to have antidepressant effects, and as result it has been proposed as a treatment for bipolar disorder as well. People with bipolar disorder generally exercise a lot less than those without, commonly falling short of the minimum healthy exercise dose recommended by the American College of Sports Medicine (150 min/week of moderate aerobic activity or 60 min/week of vigorous activity). As an intervention for bipolar disorder, exercise has clear benefits for physical comorbidities such as increased body mass and decreased cardiovascular fitness. though this includes many showing no effect. In some cases, exercise appears to correct brain structure abnormalities without measurably improving the symptoms. The most frequent side effects of ECT include memory impairment, headaches, and muscle aches. Ketogenic diet Because many of the medications that are effective in treating epilepsy are also effective as mood stabilizers, it has been suggested that the ketogenic diet—used for treating pediatric epilepsy—could have mood stabilizing effects. Ketogenic diets are diets that are high in fat and low in carbohydrates, and force the body to use fat for energy instead of sugars from carbohydrates. This causes a metabolic response similar to that seen in the body during fasting. This idea has not been tested by clinical research, and until recently, was entirely hypothetical. Recently, however, two case studies have been described where ketogenic diets were used to treat bipolar II. In each case, the patients found that the ketogenic diet was more effective for treating their disorder than medication and were able to discontinue the use of medication. The key to efficacy appears to be ketosis, which can be achieved either with a classic high-fat ketogenic diet, or with a low-carbohydrate diet similar to the induction phase of the Atkins Diet. The mechanism of action is not well understood. It is unclear whether the benefits of the diet produce a lasting improvement in symptoms (as is sometimes the case in treatment for epilepsy) or whether the diet would need to be continued indefinitely to maintain symptom remission. == See also ==