Сравнение лития и флуоксетина у больных БАР

Background
Controversy exists over antidepressant use in rapid-cycling bipolar disorder.
Aims

Exploratory analysis of safety and efficacy of fluoxetine v. lithium monotherapy in individuals with rapid- v. non-rapid-cycling bipolar II disorder.

Method

Randomised, double-blind, placebo-controlled comparison of fluoxetine v. lithium monotherapy in patients initially stabilised on fluoxetine monotherapy (trial registration NCT00044616).

Results

The proportion of participants with depressive relapse was similar between the rapid- and non-rapid-cycling groups (P = 0.20). The odds of relapse were similar between groups (P = 0.36). The hazard of relapse was similar between groups (hazard ratio 0.87, 95% CI 0.40–1.91). Change in mania rating scores was similar between groups (P = 0.86). There was no difference between groups in the rate of syndromal (P = 0.27) or subsyndromal (P = 0.82) hypomania.

Conclusions

Depressive relapse and treatment-emergent mood conversion episode rates were similar for lithium and fluoxetine monotherapy and placebo during long-term, relapse-prevention therapy of rapid- and non-rapid-cycling bipolar II disorder.

Efficacy and mood conversion rate during long-term fluoxetine v. lithium monotherapy in rapid- and non-rapid-cycling bipolar II disorder

Роль минеральных веществ в патогенезе психических расстройств

Early studies showed that women affected by chronic depression sometimes have copper, zinc, and cesium deficiencies [37,38]. Later studies suggest that the presence of depression and other neuropsychiatric symptoms is due to the deposit of copper in the central nervous system [39]. Eggers et al. [40] used SPECT to demonstrate a reduction in thalamichypothalamic presynaptic dopamine and serotonin transporters due to the accumulation of copper. There was a negative correlation between the density of presynaptic dopamine transporters and the severity of depression as assessed using the Hamilton Rating Scale for Depression.

It was recently hypothesized that trace elements play an important role in the pathogenesis of

bipolar disorders by causing neurodegeneration [41]. Moreover, essential elements like vanadium have been implicated as a causative factor for bipolar mood disorder, while elevated vanadium and molybdenum levels have been reported in serum samples from bipolar mood disorder patients [41]. This latter study showed, using DSM-IV standard diagnostic criteria and classification into types I, II, and V according to the concept of Young and Klerman, that Na, K, P, Cu, Al, and Mn were elevated significantly in Bipolar I (Mania) (P < 0.001). In Bipolar II hypomania, Na, S, Al, and Mn were increased significantly (P < 0.02), while in Bipolar II depression, Na, K, Cu, and Al were increased significantly (P < 0.001). Finally, in Bipolar V, Na, Mg, P, Cu, and Al were increased significantly (P < 0.002) compared to a control group [41]. A recent study by Gonzales-Estecha and colleagues [21] found higher serum copper and zinc, blood lead and cadmium, and urine lead, cadmium, and thallium concentrations in patients diagnosed with bipolar disorders compared to a control group.

Increased neuronal oxidative stress (OxS) induces deleterious effects on signal transduction, structural plasticity and cellular resilience, mostly by inducing lipid peroxidation in membranes, proteins and genes [42]. It has been hypothesized that these pathological processes occur in critical brain circuits that regulate affective functioning, emotions, motoric behavior and pleasure involved in bipolar disorder (BD) [43,44].

The brain is particularly vulnerable to oxidative damage since it contains large amounts of polysaturated fatty acids and possesses low antioxidant capacity [45]. Several studies have demonstrated altered OxS parameters in the pathophysiology and therapeutics of BD, including changes in the levels of enzymes superoxide dismutase (SOD), catalase (CAT) and thiobarbituric acid reactive substances (TBARS) [46]. The well-known stabilizing agent Lithium was found to limit the enzyme activity, potentially lowering hydrogen peroxide and hydroxyl radical formation. Similarly, lithium was also shown to reverse increased OxS parameters in BD [43,47]. For instance, a decline in lipid peroxidation and an increase in CAT levels were observed in valproate and lithium-treated rats [42,48]. Accumulation of copper was shown to increase oxidative stress in bivalve species [49]. In skeletal muscle of Broilers Under Heat Stress, copper decreases because of dietary Selenium, Vitamin E, and their combination with an increase in antioxidant defense [50]. In humans accumulation of copper was associated with oxidative stress in allergic asthma patients, and introduction of nutritional supplement therapy accompanies improved oxidative stress, immune response, pulmonary function, and decrease in copper plasma levels [51]. On the other hands copper levels were elevated in several brain areas in a degenerative disease such as Niemann-Pick C [52]. Interestingly, Nieman-Pick C disease was specifically indicated to be associated with Bipolar Disorders [53]. If the results of our study are further confirmed, it will lend significant support to the hypothesis that minerals such as copper play an etiological role in psychiatric disorders, and WD may serve as a pathogenic model for the bipolar disorder. 

Bipolar disorders and Wilson’s disease

Индуцированная сибутрамином мания как дебют биполярного аффективного расстройства

Background
Sibutramine, used in obesity treatment, has been associated with many neuropsychiatric side effects including hypomanic and manic episodes. Hypomanic or manic episodes related to sibutramine treatment were earlier reported in patients who had previous history of bipolar disorder, after sibutramine overdose, after over-the-counter product illegally containing very high dose of sibutramine, together with psychotic symptoms, in organic patient, or after interaction of sibutramine with other drugs.
Case presentation
We report the first case of a patient with clear manic episode, after treatment with recommended dose of sibutramine, without previous history of mood disorders, organic changes or drug interactions, that was followed by episode of depression.
Conclusion
Minimal recommended dose of sibutramine induced manic episode that was the first manifestation of bipolar disorder. The manic episode, associated with sibutramine treatment, was induced in a person without previous history of mood disorders. Potential risks associated with the treatment of obesity using sibutramine warn physicians to be alert not only to common and cardiovascular but also to psychiatric adverse effects. A careful assessment of patient's mental state and detailed psychiatric family history should be done before sibutramine treatment. In patients with a family history for bipolar disorder the use of even minimal dose of sibutramine should be contraindicated.

 Sibutramine-induced mania as the first manifestation of bipolar disorder.

Глюкокортикостероиды и риск суицида

Glucocorticoid medications given in primary care settings are associated with suicidal behaviors and severe neuropsychiatric disorders, new research suggests.

In a large, population-based study of adult patients in the United Kingdom (UK), those receiving glucocorticoids were almost 7 times more likely to commit or attempt suicide, more than 5 times more likely to develop delirium, more than 4 times more likely to develop mania, and almost twice as likely to develop depression than those with the same underlying conditions who did not receive the medications.

In addition, patients younger than 30 years were at particular risk for suicide attempts, women were more at risk for depression, and men were at especially increased risk for mania and delirium/confusion/disorientation. Higher dosages of the medications were also linked to an overall greater risk for adverse outcomes.

 Glucocorticoids Linked to Suicide, Neuropsychiatric Disorders

Оланзапин при резистентной мании

Objective

To examine the safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania.
Method

Subjects (n = 18) who were acutely manic, did not respond to lithium, anticonvulsants, and neuroleptics, and/or had intolerable side effects to them in previous manic episodes were openly treated with olanzapine monotherapy (5–40 mg/d) for 12 weeks. The primary and secondary outcomes included the change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score, Clinical Global Impression for Bipolar Disorder-Severity Scale (CGI-S), 17-item Hamilton Depression Rating Scale (HAM-D) and Positive and Negative Syndrome Scale (PANSS), and response and remission rate.
Results

The mean change in YMRS total score from baseline to endpoint was −23.3 ± 8.4 (p < 0.001). Fifteen (88.5%) patients achieved response (≥50% reduction in YMRS total score) and 14 (77.8%) achieved remission (YMRS total score ≤9 at endpoint). Mean changes from baseline to endpoint in CGI-S for mania and PANSS total score were significant, but not the changes in HAM-D total score or CGI-S for depression. The most common adverse events were sedation, self-reported weight gain, ≥7% increase in body weight, dizziness, and akathisia.

Safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania: a 12-week open-label study

Психические расстройства при гипотиреозе и гипертиреозе

The symptoms and signs of hyperthyroidism resemble those of primary mental disorders. Overactivity of the adrenergic system caused by hyperthyroidism may explain the similarity between the clinical presentations of hyperthyroidism and mania or anxiety, as well as the precipitating role of hyperthyroidism in the development of mania or anxiety disorder. It may also explain the increased sense of well being often experienced in the early stages of hyperthyroidism.[20,21]

The relationship between hyperthyroidism and depression is less clear. Depression is usually linked to hypothyroidism, not to hyperthyroidism. However, prolonged hyperthyroidism might exhaust noradrenergic transmission and thus contribute to depression. Noradrenergic exhaustion might well occur in patients with hyperthyroidism who have bipolar disorder. In the initial phase of hyperthyroidism, thyroid hormone stimulation of the noradrenergic system may cause mania; later, when noradrenergic neurotransmission is exhausted, it may contribute to depression.[21]

Mental symptoms and disorders secondary to hyperthyroidism should be treated first by restoring euthyroidism. Most mental symptoms, including depression, usually resolve once euthyroidism has been regained. Treatment with beta-adrenergic antagonists alone may quickly relieve many symptoms, including mental symptoms, even if euthyroidism is not restored,[22] providing evidence that overactivity of the adrenergic system is largely responsible for mental symptoms in hyperthyroidism.

Thyroid deficits are frequently observed in bipolar patients, especially in women with the rapid cycling form of the disease.[24] Both subclinical hypothyroidism and subclinical hyperthyroidism increase the risk for Alzheimer's disease, especially in women.[25] However, most hypothyroid patients do not meet the criteria for a mental disorder.

A recent study evaluated brain glucose metabolism during T4 treatment of hypothyroidism. A reduction in depression and cognitive symptoms was associated with restoration of metabolic activity in brain areas that are integral to the regulation of mood and cognition.[26••]

In hypothyroidism, replacement therapy with T4 remains the treatment of choice and resolves most physical and psychological signs and symptoms in most patients. However, some patients do not feel entirely well despite doses of T4 that are usually adequate.[27] In T4-treated patients, it was found that reduced psychological well being is associated with occurrence of polymorphism in the D2 gene,[28••] as well as in the OATP1c1 gene.[29]

Thyroid hormone replacement with a combination of T4 and T3, in comparison with T4 monotherapy, improves mental functioning in some but not all hypothyroid patients,[30,31•] and most of the patients subjectively prefer combined treatment.[32] Two studies have evaluated whether D2 polymorphism is associated with changes in psychological well being after combined T4 and T3 treatment. One underpowered study[33] reported a trend toward improvement. In a second study[28••] involving a very large sample, D2 polymorphism was associated with improvement in psychological well being after T4 and T3 treatment.

Thyroid Disease and Mental Disorders: Cause and Effect or Only comorbidity?

Маниакальная симптоматика ассоциированная с приступами мигрени

This is a case report of a previously diagnosed "treatment-refractory bipolar" patient whose successful treatment of atypical migraine resulted in the questioning of any psychiatric diagnosis.

A 47-year-old man was referred to the Mood Disorders Clinic for severe migraine associated with mood, "psychic," and neurologic symptoms. He had first presented to Psychiatry 8 years earlier, for acute "mania" with agitation, extreme lability, intense anger, and religiosity necessitating hospitalization. Subsequently, he had recurrences of similar manic "crises" followed by a "depressive" states consisting of cognitive dysfunction, avolition, and anhedonia. He also experienced severe headache and nonspecific neurological symptoms. A diagnosis of migraine was suspected, and a thorough neurological work-up did not yield other diagnoses. Medical history revealed multiple recurrent migraine-equivalents since childhood (particularly, abdominal pain).

Each psychiatric "crisis" was preceded by weeks of increasingly frequent, severe, early morning migraine attacks, with subsequent sleep deprivation, and intensification of migraine symptoms, including aura, with disorganized speech and thinking and bizarre behavior. A prolonged period of complete rest would break the cycle of migraine, accompanied by complete resolution of psychiatric symptoms.

Previous treatments included lithium, buproprion, as well as nortriptyline, stemetil, valproic acid, and quetiapine, none of which were helpful. Family history was positive for migraine and negative for psychiatric disorders. On referral, his medications were propranolol 40 mg twice daily, valproic acid 500 mg twice daily, and lamotrigine 100 mg twice daily. Valproic acid level was therapeutic. A diagnosis of mood disorder, bipolar type secondary to severe migraine was made.

Discussion

This case illustrates the importance of inquiry of neurological symptoms, in particular headache, in patients with bipolar disorder. Patients with bipolar disorder have a greater-than-twofold risk of having migraine, as compared with the general population.1 Treatment for migraine, irrespective of mood disorder, includes amitriptyline, valproate, topiramate, and beta-blockers.2 In patients with bipolar disorder and migraine, judicious use of treatments for both disorders should be considered. Lamotrigine was used for this patient because valproate, although approved for both disorders,3 did not ameliorate the migraine symptoms. For bipolar disorder, lamotrigine is efficacious in the prevention of depressive episodes and, possibly, rapid-cycling type.4 Less evidence supports its use in acute depression or mania.4 For migraine, lamotrigine was not beneficial in a placebo-controlled trial, but had some effectiveness in two open pilot studies for the treatment and prevention of migraine aura.2

Lamotrigine is generally well tolerated, with an acceptable side-effects profile (mainly dizziness, nausea, and insomnia), and may be considered for a patient with aura nonresponsive to other medication. Slow and low dose increase is recommended for side-effects monitoring, especially for severe rashes and Steven's Johnson syndrome. In our patient, lamotrigine was increased to 200 mg twice daily. Use of lamotrigine with valproate may increase lamotrigine concentrations by up to 200% because of increased lamotrigine clearance inhibition,3,5 and valproate levels may also decrease.3 The patient's headache duration eventually decreased to 1 hour nightly, and he returned to work full-time with a 45-minute nap.

Atypical Migraine Manifesting as Mania

Случай ухудшения маниакальной симптоматики при приёме низких доз кветиапина

The mechanism of antidepressant action of quetiapine is unclear. However, it has been suggested that its antidepressant activity is mediated by its metabolite N-Desalkylquetiapine, which leads to norepinephrine reuptake transporter inhibition and partial serotonin 1A agonism.4 A speculation may be that slow clearance of the metabolites as an age effect or genetic trait in this case led to very high levels of N-Desalkylquetiapine potentiating quetiapine's antidepressant effect and leading to worsening of mania. Moreover, a positron emission tomography (PET) study using quetiapine 750 mg or 450 mg/day found that there was no D2 receptor occupancy at the low dose of quetiapine, while 5HT2A receptor occupancy was consistently high.5 Despite the normal head CT scan, brain-aging related neurotransmitter changes and therefore different medication effects could be considered. Calabrese et al.1 reported an incidence of treatment-emergent mania 2.2% with 600 mg/day of quetiapine and 3.9% with 300 mg/day of quetiapine. The absence of dopaminergic receptors blockade and the high affinity for serotonergic receptors at lower doses, may explain quetiapine's antidepressant activity and worsening mania in case of slow titration in manic patients. In this case, geriatrician treatment practice of "start low and go slow" raised questions.

Worsening Mania Associated With Slow Increase of Quetiapine Dose

Аффективные расстройства быстрого цикла ассоциированные с менструальным циклом

Affective fluctuations during menstruation have drawn considerable interest from researchers for a long time.1 Data indicates increased frequency of depression associated with menstrual period in adolescence,2 though there is limited information about the differences in the course or symptoms of bipolar disorder associated with menstrual period in adolescents. The question of the direction of mood shifts in the course of bipolar disorder with specific phases of menstrual cycle has been raised, albeit with limited and inconsistent results.3 We present a case of an adolescent female with cyclic affective changes akin to rapid cycling bipolar disorder starting in the premenstrual (luteal) period and subsiding with onset of menstruation, and we try to explore the biological underpinnings of inherent propensity for the development of bipolar disorder using quantitative electroencephalography (qEEG)

There was high spectral power in low frequency (theta band) over the right temporal region which was further corroborated by LORETA and revealed high signal density over the right temporal region for the same frequency band

A review3 presented findings of 24 prospective studies of affective fluctuations during the menstrual cycle. In most cases the authors found that negative moods marked by irritability, restlessness, anxiety, tension, migraine, sleep disturbance, and impaired concentration occurred more often during the premenstrual and menstrual phases than at other times in the cycle. There were only a few cases of positive moods—such as an increased feeling of well-being, elation, pleasantness, and activation—during the follicular and midcycle phases.3 This case presents with positive mood state, though irritability and headache were present as seen in premenstrual syndrome (PMS). This is an atypical presentation of PMS as opposed to the more common occurrence of elated moods during midcycle; in our case it occurred in premenstrual phase.7 It has been reported that whereas menstrual problems appear to occur more frequently in younger than in older women, premenstrual symptoms occur more often in older women. This suggests a relation between age and menstrual symptoms.

The overlap in symptomatology between PMS and cyclothymia, often considered to be a variant of manic-depressive illness, has given rise to therapeutic trials of lithium carbonate in women with PMS, with mixed results.14 Lithium treatment has been beneficial in controlling premenstrual affective changes, and this led us to use the same in our case.

Rapid Cycling Associated With Menstrual Periods in an Adolescent: Electrophysiological Underpinnings for Bipolarity

Инверсия аффекта - дозозависимый эффект бупропиона

A switch into mania is a potential risk associated with antidepressant drug use in bipolar affective disorder. Bupropion is believed to be associated with a decreased risk compared with other antidepressant therapies. However, our case report as well as others support the theory that this decreased risk may be due to dosages not exceeding the recommended daily dose (450 mg/d). Doses of bupropion >450 mg/d should be used with caution in depressed patients with bipolar affective disorder.

Mania with bupropion: a dose-related phenomenon?

Распространённость и факторы риска развития маниакальных и гипоманиакальных состояний при терапии антидепрессантами

Antidepressant-induced manias have been reported with all major antidepressant classes in a subgroup of about 20-40% of bipolar patients. Lithium may confer better protection against this outcome when compared with other standard mood stabilizers, although switch rates have been reported with comparable frequencies on or off mood stabilizers. Evidence across studies most consistently supports an elevated risk in patients with (i) previous antidepressant-induced manias, (ii) a bipolar family history, and (iii) exposure to multiple antidepressant trials.

ANTIDEPRESSANT-INDUCED MANIA: AN OVERVIEW OF CURRENT CONTROVERSIES

Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008).

Antidepressant-induced mania in bipolar patients: identification of risk factors.

Antidepressant-induced mania or hypomania was evident in 39.6% (21/53) of the study group. Patients who developed manic features soon after starting an antidepressant had more antidepressant trials per year than those who did not (p < .05). A history of substance abuse and/or dependence was associated with substantially increased risk for antidepressant-induced mania (odds ratio = 6.99, 95% CI = 1.57 to 32.28, p = .007). Concomitant mood stabilizers were not uniformly associated with protection against inductions of mania during antidepressant trials.

The association between substance abuse and antidepressant-induced mania in bipolar disorder: a preliminary study

Аффективные расстройства лекарственного генеза

Causes

* Drugs with evidence of a link to depression or mania include the following:
o Flunarizine - Epidemiologic survey, adverse effect noted in several clinical trials
o Corticosteroids - Prospective cohort study, cross-sectional medicine patients
o Digoxin - Prospective cohort study, cross-sectional epidemiologic study
o Minor tranquilizers - Prospective cohort study
o Sedatives - Prospective cohort study
o Interferon beta-1b, peginterferon alfa-2b - Very significantly increased incidence in randomized controlled trials (RCTs), although trials were not designed to study this as an endpoint
o Amantadine - Increased incidence in RCTs, although trials were not designed to study this as an endpoint
o Isocarboxazid - Increased incidence in RCTs, although trials were not designed to study this as an endpoint
o Levetiracetam - Increased incidence in RCTs, although trials were not designed to study this as an endpoint

* Drugs with weak or conflicting evidence of a link to depression or mania include the following:
o ACE inhibitors - Prescription sequence symmetry analysis
o Propranolol and nadolol (ie, lipophilic beta-blockers) - Meta-analysis of antihypertensive clinical trials, record linkage studies
o Norplant - Series of case reports
o Leuprolide - Case series
o Isotretinoin - Case reports
o Antidepressants (ie, citalopram, bupropion, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, sertraline, venlafaxine) - Case reports

Differential Diagnoses

Adjustment Disorders
Alcoholism
Anxiety Disorders
Dysthymic Disorder
Hypothyroidism
Other Problems to Be Considered

Adrenal Insufficiency and Adrenal Crisis
Delirium, Dementia, and Amnesia

Substance-Induced Mood Disorders, Depression and Mania

Психические расстройства при гипотиреозе и гипертиреозе

The symptoms and signs of hyperthyroidism resemble those of primary mental disorders. Overactivity of the adrenergic system caused by hyperthyroidism may explain the similarity between the clinical presentations of hyperthyroidism and mania or anxiety, as well as the precipitating role of hyperthyroidism in the development of mania or anxiety disorder. It may also explain the increased sense of well being often experienced in the early stages of hyperthyroidism.[20,21]

The relationship between hyperthyroidism and depression is less clear. Depression is usually linked to hypothyroidism, not to hyperthyroidism. However, prolonged hyperthyroidism might exhaust noradrenergic transmission and thus contribute to depression. Noradrenergic exhaustion might well occur in patients with hyperthyroidism who have bipolar disorder. In the initial phase of hyperthyroidism, thyroid hormone stimulation of the noradrenergic system may cause mania; later, when noradrenergic neurotransmission is exhausted, it may contribute to depression.[21]

Mental symptoms and disorders secondary to hyperthyroidism should be treated first by restoring euthyroidism. Most mental symptoms, including depression, usually resolve once euthyroidism has been regained. Treatment with beta-adrenergic antagonists alone may quickly relieve many symptoms, including mental symptoms, even if euthyroidism is not restored,[22] providing evidence that overactivity of the adrenergic system is largely responsible for mental symptoms in hyperthyroidism.

Thyroid deficits are frequently observed in bipolar patients, especially in women with the rapid cycling form of the disease.[24] Both subclinical hypothyroidism and subclinical hyperthyroidism increase the risk for Alzheimer's disease, especially in women.[25] However, most hypothyroid patients do not meet the criteria for a mental disorder.

A recent study evaluated brain glucose metabolism during T4 treatment of hypothyroidism. A reduction in depression and cognitive symptoms was associated with restoration of metabolic activity in brain areas that are integral to the regulation of mood and cognition.[26••]

In hypothyroidism, replacement therapy with T4 remains the treatment of choice and resolves most physical and psychological signs and symptoms in most patients. However, some patients do not feel entirely well despite doses of T4 that are usually adequate.[27] In T4-treated patients, it was found that reduced psychological well being is associated with occurrence of polymorphism in the D2 gene,[28••] as well as in the OATP1c1 gene.[29]

Thyroid hormone replacement with a combination of T4 and T3, in comparison with T4 monotherapy, improves mental functioning in some but not all hypothyroid patients,[30,31•] and most of the patients subjectively prefer combined treatment.[32] Two studies have evaluated whether D2 polymorphism is associated with changes in psychological well being after combined T4 and T3 treatment. One underpowered study[33] reported a trend toward improvement. In a second study[28••] involving a very large sample, D2 polymorphism was associated with improvement in psychological well being after T4 and T3 treatment.

Thyroid Disease and Mental Disorders: Cause and Effect or Only comorbidity?

Временные обрывы маниакального состояния вестибулярной стимуляцией

Caloric vestibular stimulation is a common clinical procedure, routinely employed during testing of vestibulocochlear nerve function. The procedure involves stimulation of vestibular afferents by the application of cooled water to the tympanic membrane. Vestibular afferents are distributed widely to areas of the diencephalon and cortex, including areas believed to be involved in the regulation of mood. In accordance with these observations, imaging studies have shown widespread though largely contralateral hemispheric activation following the procedure.

Vestibular stimulation in mania: acase report