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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.
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.
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.
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.
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.
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.
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 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.
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.
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
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.
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.
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.
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.
A 2010 review by the Cochrane collaboration found that no medications show promise for "the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment". However, the authors found that some medications may impact isolated symptoms associated with BPD or the symptoms of comorbid conditions. A 2017 review examined evidence published since the 2010 Cochrane review and found that "evidence of effectiveness of medication for BPD remains very mixed and is still highly compromised by suboptimal study design".
Of the typical antipsychotics studied in relation to BPD, haloperidol may reduce anger and flupenthixol may reduce the likelihood of suicidal behavior. Among the atypical antipsychotics, one trial found that aripiprazole may reduce interpersonal problems and impulsivity. Olanzapine may decrease affective instability, anger, psychotic paranoid symptoms, and anxiety, but a placebo had a greater ameliorative impact on suicidal ideation than olanzapine did. The effect of ziprasidone was not significant.
Of the mood stabilizers studied, valproate semisodium may ameliorate depression, interpersonal problems, and anger. Lamotrigine may reduce impulsivity and anger; topiramate may ameliorate interpersonal problems, impulsivity, anxiety, anger, and general psychiatric pathology. The effect of carbamazepine was not significant. Of the antidepressants, amitriptyline may reduce depression, but mianserin, fluoxetine, fluvoxamine, and phenelzine sulfate showed no effect. Omega-3 fatty acid may ameliorate suicidality and improve depression. As of 2017, trials with these medications had not been replicated and the effect of long-term use had not been assessed.
Because of weak evidence and the potential for serious side effects from some of these medications, the UK National Institute for Health and Clinical Excellence (NICE) 2009 clinical guideline for the treatment and management of BPD recommends, "Drug treatment should not be used specifically for borderline personality disorder or for the individual symptoms or behavior associated with the disorder." However, "drug treatment may be considered in the overall treatment of comorbid conditions". They suggest a "review of the treatment of people with borderline personality disorder who do not have a diagnosed comorbid mental or physical illness and who are currently being prescribed drugs, with the aim of reducing and stopping unnecessary drug treatment".
Psychotherapy is the primary treatment for borderline personality disorder. Treatments should be based on the needs of the individual, rather than upon the general diagnosis of BPD. Medications are useful for treating comorbid disorders, such as depression and anxiety. Short-term hospitalization has not been found to be more effective than community care for improving outcomes or long-term prevention of suicidal behavior in those with BPD.
Benzodiazepines, such as alprazolam, clonazepam, lorazepam and diazepam, can cause both depression and mania.
Benzodiazepines are a class of medication commonly used to treat anxiety, panic attacks and insomnia, and are also commonly misused and abused. Those with anxiety, panic and sleep problems commonly have negative emotions and thoughts, depression, suicidal ideations, and often have comorbid depressive disorders. While the anxiolytic and hypnotic effects of benzodiazepines disappear as tolerance develops, depression and impulsivity with high suicidal risk commonly persist. Unfortunately, these symptoms are “often interpreted as an exacerbation or as a natural evolution of previous disorders and the chronic use of sedatives is overlooked.” Benzodiazepines do not prevent the development of depression, can exacerbate preexisting depression, can cause depression in those with no history of it, and can lead to suicide attempts. Risk factors for attempted and completed suicide while using benzodiazepines include high dose prescriptions (even in those not misusing the medications), benzodiazepine intoxication, and underlying depression.
The long-term use of benzodiazepines may have a similar effect on the brain as alcohol, and are also implicated in depression. As with alcohol, the effects of benzodiazepine on neurochemistry, such as decreased levels of serotonin and norepinephrine, are believed to be responsible for the increased depression. Additionally, benzodiazepines can indirectly worsen mood by worsening sleep (i.e., benzodiazepine-induced sleep disorder). Like alcohol, benzodiazepines can put people to sleep but, while asleep, they disrupt sleep architecture: decreasing sleep time, delaying time to REM sleep, and decreasing deep sleep (the most restorative part of sleep for both energy and mood). Just as some antidepressants can cause or worsen anxiety in some patients due to being activating, benzodiazepines can cause or worsen depression due to being a central nervous system depressant—worsening thinking, concentration and problem solving (i.e., benzodiazepine-induced neurocognitive disorder). However, unlike antidepressants, in which the activating effects usually improve with continued treatment, benzodiazepine-induced depression is unlikely to improve until after stopping the medication.
In a long-term follow-up study of patients dependent on benzodiazepines, it was found that 10 people (20%) had taken drug overdoses while on chronic benzodiazepine medication despite only two people ever having had any pre-existing depressive disorder. A year after a gradual withdrawal program, no patients had taken any further overdoses.
Just as with intoxication and chronic use, benzodiazepine withdrawal can also cause depression. While benzodiazepine-induced depressive disorder may be exacerbated immediately after discontinuation of benzodiazepines, evidence suggests that mood significantly improves after the acute withdrawal period to levels better than during use. Depression resulting from withdrawal from benzodiazepines usually subsides after a few months but in some cases may persist for 6–12 months.
A major option for many mental disorders is psychiatric medication and there are several main groups. Antidepressants are used for the treatment of clinical depression, as well as often for anxiety and a range of other disorders. Anxiolytics (including sedatives) are used for anxiety disorders and related problems such as insomnia. Mood stabilizers are used primarily in bipolar disorder. Antipsychotics are used for psychotic disorders, notably for positive symptoms in schizophrenia, and also increasingly for a range of other disorders. Stimulants are commonly used, notably for ADHD.
Despite the different conventional names of the drug groups, there may be considerable overlap in the disorders for which they are actually indicated, and there may also be off-label use of medications. There can be problems with adverse effects of medication and adherence to them, and there is also criticism of pharmaceutical marketing and professional conflicts of interest.
Often in those who have experienced their first episode of hypomania – generally without psychotic features – there may be a long or recent history of depression or a mix of hypomania combined with depression (known as mixed-state) prior to the emergence of manic symptoms. This commonly surfaces in the mid to late teens. Because the teenage years are typically an emotionally charged time of life, it is not unusual for mood swings to be passed off as normal hormonal teen behavior and for a diagnosis of bipolar disorder to be missed until there is evidence of an obvious manic or hypomanic phase.
Hypomania may also occur as a side effect of pharmaceuticals prescribed for conditions or diseases other than psychological states or mood disorders. In those instances, as in cases of drug-induced hypomanic episodes in unipolar depressives, the hypomania can almost invariably be eliminated by lowering medication dosage, withdrawing the drug entirely, or changing to a different medication if discontinuation of treatment is not possible.
Hypomania may also be triggered by the occurrence of a highly exciting event in the patient's situation, such as a substantial financial gain or recognition.
Hypomania can be associated with narcissistic personality disorder.
In patients suffering from schizophrenia, grandiose and religious delusions are found to be the least susceptible to cognitive behavioral interventions. Cognitive behavioral intervention is a form of psychological therapy, initially used for depression, but currently used for a variety of different mental disorders, in hope of providing relief from distress and disability. During therapy, grandiose delusions were linked to patients' underlying beliefs by using inference chaining. Some examples of interventions performed to improve the patient's state were focus on specific themes, clarification of neologisms, and thought linkage. During thought linkage, the patient is asked repeatedly by the therapist to explain his/her jumps in thought from one subject to a completely different one.
Patients suffering from mental disorders that experience grandiose delusions have been found to have a lower risk of having suicidal thoughts and attempts.
Electroconvulsive therapy (ECT) is sometimes used in severe cases when other interventions for severe intractable depression have failed. Psychosurgery is considered experimental but is advocated by some neurologists in certain rare cases.
Counseling (professional) and co-counseling (between peers) may be used. Psychoeducation programs may provide people with the information to understand and manage their problems. Creative therapies are sometimes used, including music therapy, art therapy or drama therapy. Lifestyle adjustments and supportive measures are often used, including peer support, self-help groups for mental health and supported housing or supported employment (including social firms). Some advocate dietary supplements.
Reasonable accommodations (adjustments and supports) might be put in place to help an individual cope and succeed in environments despite potential disability related to mental health problems. This could include an emotional support animal or specifically trained psychiatric service dog.
Mania and hypomania are usually studied together as components of bipolar disorders, and the pathophysiology is usually assumed to be the same. Given that norepinephrine and dopaminergic drugs are capable of triggering hypomania, theories relating to monoamine hyperactivity have been proposed. A theory unifying depression and mania in bipolar individuals proposes that decreased serotonergic regulation of other monoamines can result in either depressive or manic symptoms. Lesions on the right side frontal and temporal lobes have further been associated with mania.
In a mixed affective state, the individual, though meeting the general criteria for a hypomanic (discussed below) or manic episode, experiences three or more concurrent depressive symptoms. This has caused some speculation, among clinicians, that mania and depression, rather than constituting "true" polar opposites, are, rather, two independent axes in a unipolar—bipolar spectrum.
A mixed affective state, especially with prominent manic symptoms, places the patient at a greater risk for completed suicide. Depression on its own is a risk factor but, when coupled with an increase in energy and goal-directed activity, the patient is far more likely to act with violence on suicidal impulses.