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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.
Few medications are approved specifically for schizoaffective disorder. In general, medications are chosen to reduce symptoms of psychosis and mood disorder.
Antipsychotic medication is usually required both for acute treatment and the prevention of relapse. There is no single antipsychotic of choice in treating schizoaffective disorder, but atypical antipsychotics should be considered because they have mood-stabilizing activity. Paliperidone is an antipsychotic with FDA approval for the treatment of schizoaffective disorder. Antipsychotics should be used at the minimum dose necessary to control symptoms. Potential side effects include extrapyramidal symptoms, including tremor, muscle stiffness, and restlessness or akathisia. Atypical antipsychotics carry a risk of metabolic syndrome, including weight gain, increased blood sugar, and increased blood cholesterol, so regular monitoring of weight and bloodwork should be carried out. Some atypical antipsychotics, such as ziprasidone and aripiprazole, are associated with less risk than others, such as olanzapine. Medication choice is based on how effectively it reduces symptoms, how few side effects it causes, and cost.
In people with treatment-refractory psychosis, a clozapine trial should be considered. Clozapine is an atypical antipsychotic that is recognized as being particularly effective when other antipsychotic agents have failed. Clozapine should also be considered in people with chronic and persistent suicidal thinking and behaviour, as it has been shown to reduce the risk of suicide in patients with schizoaffective disorder and a history of suicidality. Between 0.5 and 2% of patients taking clozapine may develop a life-threatening complication called agranulocytosis, which is a significant drop in a type of white blood cell. Because of this risk, people taking clozapine must have regular monitoring of blood cell counts.
The management of the bipolar type of schizoaffective disorder is similar to the treatment of bipolar disorder, with the goal of preventing mood episodes and cycling. Lithium or anticonvulsant mood stabilizers such as valproic acid, carbamazepine, and lamotrigine are prescribed in combination with an antipsychotic.
For depression, if an antidepressant is prescribed, "extra attentiveness must be given" by the prescribing clinician due its risk for long-term mood cycle acceleration (that is, inducing more frequent episodes of depression per unit of time) and medication-induced psychosis or mania. For individuals who show emerging psychosis, mania, mixed episode symptoms, or mood cycle acceleration, switching to an antipsychotic plus lithium or lamotrigine is preferable to antidepressants.
For individuals who experience anxiety, anti-anxiety medications can be used, usually on a short-term basis. Benzodiazepines, including lorazepam, clonazepam and diazepam, are types of anti-anxiety medications. Care must be taken when prescribing benzodiazepines due to the risk of the patient developing tolerance and dependence.
Mood stabilizers are often used as part of the treatment process.
1. Lithium is the mainstay in the management of bipolar disorder but it has a narrow therapeutic range and typically requires monitoring
2. Anticonvulsants, such as sodium valproate, carbamazepine or lamotrigine
3. Antipsychotics, such as quetiapine, risperidone, olanzapine or aripiprazole
4. Electroconvulsive therapy, a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect
Some antidepressants, like venlafaxine, have been found to precipitate a manic episode.
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.
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.
Electroconvulsive therapy, or ECT, may be considered for patients with schizoaffective disorder experiencing severe depression or severe psychotic symptoms that have not responded to treatment with antipsychotics.
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.
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.
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.
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.
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
Information on the condition, importance of regular sleep patterns, routines and eating habits and the importance of compliance with medication as prescribed. Behavior modification through counseling can have positive influence to help reduce the effects of risky behavior during the manic phase. Additionally, the lifetime prevalence for bipolar I disorder is estimated to be 1%.
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.
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.
Before beginning treatment for mania, careful differential diagnosis must be performed to rule out secondary causes.
The acute treatment of a manic episode of bipolar disorder involves the utilization of either a mood stabilizer (valproate, lithium, or carbamazepine) or an atypical antipsychotic (olanzapine, quetiapine, risperidone, or aripiprazole). Although hypomanic episodes may respond to a mood stabilizer alone, full-blown episodes are treated with an atypical antipsychotic (often in conjunction with a mood stabilizer, as these tend to produce the most rapid improvement).
When the manic behaviours have gone, long-term treatment then focuses on prophylactic treatment to try to stabilize the patient's mood, typically through a combination of pharmacotherapy and psychotherapy. The likelihood of having a relapse is very high for those who have experienced two or more episodes of mania or depression. While medication for bipolar disorder is important to manage symptoms of mania and depression, studies show relying on medications alone is not the most effective method of treatment. Medication is most effective when used in combination with other bipolar disorder treatments, including psychotherapy, self-help coping strategies, and healthy lifestyle choices.
Lithium is the classic mood stabilizer to prevent further manic and depressive episodes. A systematic review found that long term lithium treatment substantially reduces the risk of bipolar manic relapse, by 42%. Anticonvulsants such as valproate, oxcarbazepine and carbamazepine are also used for prophylaxis. More recent drug solutions include lamotrigine, which is another anticonvulsant. Clonazepam (Klonopin) is also used. Sometimes atypical antipsychotics are used in combination with the previous mentioned medications as well, including olanzapine (Zyprexa) which helps treat hallucinations or delusions, Asenapine (Saphris, Sycrest), aripiprazole (Abilify), risperidone, ziprasidone, and clozapine which is often used for people who do not respond to lithium or anticonvulsants.
Verapamil, a calcium-channel blocker, is useful in the treatment of hypomania and in those cases where lithium and mood stabilizers are contraindicated or ineffective. Verapamil is effective for both short-term and long-term treatment.
Antidepressant monotherapy is not recommended for the treatment of depression in patients with bipolar disorders I or II, and no benefit has been demonstrated by combining antidepressants with mood stabilizers in these patients.
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.
Individual approaches to treatment are recommended, usually involving a combination of mood stabilizers and atypical antipsychotics. Psychotherapy may be beneficial and should be started early.
Both psychotherapy as well as different drugs (e.g. serotonin reuptake inhibitors - SSRIs or mood stabilizers, e.g. lithium, antiepileptics) have been suggested as treatments. However, no randomized controlled treatment trial of RBD has been conducted.
There are currently no antidepressants that are FDA approved for use during lactation. Most antidepressants are excreted in breast milk. However, there are limited studies showing the effects and safety of these antidepressants on breastfed babies.
There have been a few studies of medications for treating PPD, however, the sample sizes were small, thus evidence is generally weak. Some evidence suggests that mothers with PPD will respond similarly to people with major depressive disorder. There is evidence which suggests that selective serotonin reuptake inhibitors (SSRIs) are effective treatment for PPD. However, a recent study has found that adding sertraline, an SSRI, to psychotherapy does not appear to confer any additional benefit. Therefore, it is not completely clear which antidepressants, if any, are most effective for treatment of PPD, and for whom antidepressants would be a better option than non-pharmacotherapy.
Some studies show that hormone therapy may be effective in women with PPD, supported by the idea that the drop in estrogen and progesterone levels post-delivery contribute to depressive symptoms. However, there is some controversy with this form of treatment because estrogen should not be given to people who are at higher risk of blood clots, which include women up to 12 weeks after delivery. Additionally, none of the existing studies included women who were breastfeeding.
The treatment of psychosis depends on the specific diagnosis (such as schizophrenia, bipolar disorder or substance intoxication). The first-line psychiatric treatment for many psychotic disorders is antipsychotic medication, which can reduce the positive symptoms of psychosis in about 7 to 14 days.
The choice of which antipsychotic to use is based on benefits, risks, and costs. It is debatable whether, as a class, typical or atypical antipsychotics are better. Tentative evidence supports that amisulpride, olanzapine, risperidone and clozapine may be more effective for positive symptoms but result in more side effects. Typical antipsychotics have equal drop-out and symptom relapse rates to atypicals when used at low to moderate dosages. There is a good response in 40–50%, a partial response in 30–40%, and treatment resistance (failure of symptoms to respond satisfactorily after six weeks to two or three different antipsychotics) in 20% of people. Clozapine is an effective treatment for those who respond poorly to other drugs ("treatment-resistant" or "refractory" schizophrenia), but it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.
Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of extrapyramidal side effects while some atypicals are associated with considerable weight gain, diabetes and risk of metabolic syndrome; this is most pronounced with olanzapine, while risperidone and quetiapine are also associated with weight gain. Risperidone has a similar rate of extrapyramidal symptoms to haloperidol.
Treatment is attempted through both cognitive behavioral therapy and psychotropic medication regimens, though the pharmaceutical options have shown limited success. Therapy aids in helping the patient recognize the impulses in hopes of achieving a level of awareness and control of the outbursts, along with treating the emotional stress that accompanies these episodes. Multiple drug regimens are frequently indicated for IED patients. Cognitive Relaxation and Coping Skills Therapy (CRCST) has shown preliminary success in both group and individual settings compared to waitlist control groups. This therapy consists of 12 sessions, the first three focusing on relaxation training, then cognitive restructuring, then exposure therapy. The final sessions focus on resisting aggressive impulses and other preventative measures.
Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, fluvoxamine, and sertraline appear to alleviate some pathopsychological symptoms. GABAergic mood stabilizers and anticonvulsive drugs such as gabapentin, lithium, carbamazepine, and divalproex seem to aid in controlling the incidence of outbursts. Anxiolytics help alleviate tension and may help reduce explosive outbursts by increasing the provocative stimulus tolerance threshold, and are especially indicated in patients with comorbid obsessive-compulsive or other anxiety disorders. However, certain anxiolytics are known to "increase" anger and irritability in some individuals, especially benzodiazepines.
Depressed mood may not require professional treatment, and may be a normal temporary reaction to life events, a symptom of some medical condition, or a side effect of some drugs or medical treatments. A prolonged depressed mood, especially in combination with other symptoms, may lead to a diagnosis of a psychiatric or medical condition which may benefit from treatment. Different sub-divisions of depression have different treatment approaches.
In the United States, it has been estimated that two thirds of people with depression do not actively seek treatment. The World Health Organisation (WHO) has predicted that by 2030, depression will account for the highest level of disability accorded any physical or mental disorder in the world (WHO, 2008).
The UK National Institute for Health and Care Excellence (NICE) 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, because the risk-benefit ratio is poor. A recent meta-analysis also indicated that most antidepressants, besides fluoxetine, do not seem to offer a clear advantage for children and adolescents in the acute treatment of major depressive disorder.