Van Gogh’s last work painted on the morning before he shot himself, is called Tree Roots. Many postulate that this unfinished work of art is testament to the emotional turmoil he experienced, which ultimately led to his suicide.
Suicide is often a sign of severe psychiatric disease. Suicidal behaviour is quite frequent among patients with BMD, as up to 4%–19% ultimately end their life by suicide, while 20%–60% attempt suicide at least once in their lifetime.
In BMD, the risk of suicide death is up to 10–30 times higher than that of the general population. The estimated annual suicide rate in patients with BMD is about 200–400 per 100 000. BMD-associated cases account for about 3%–14% of all suicide deaths.
What is BMD?
BMD is defined as a brain disorder that causes changes in a person’s mood, energy levels and ability to function, according to the authors of the 2020 Council for Medical Scheme’s (CMS) prescribed minimum benefits (PMBs) definition guidelines for BMD.
BMD is characterised by episodes of mania, hypomania, or depression. A person living with BMD will have severe mood swings, which can last several weeks, months or a longer period.
Changes in mood is severe enough to cause difficulties or impairment in the person’s ability to function at work, with friends or family or other important areas in their life.
A manic episode is an emotional state where a person is unusually irritable in an extreme way, most of the day for most days, has more energy than usual for at least one week. The change in mood is uncharacteristic of the person’s usual state or behaviour. A hypomanic episode is similar to a manic episode.
However, the symptoms are less severe and may only last four consecutive days.
During a depressive episode, the person experiences depressed mood (feeling sad, irritable, empty) or a loss of pleasure or interest in activities, for most of the day, nearly every day, for at least two weeks. Several other symptoms are also present, which may include poor concentration, feelings of excessive guilt or low self-worth, hopelessness about the future, thoughts about dying or suicide, disrupted sleep, changes in appetite or weight, and feeling especially tired or low in energy.
Table 1: Types of BMD
Table 2: Symptoms of BMD
Does van Gogh meet the diagnostic criteria for BMD?
Family described van Gogh as being melancholic from a young age. In his later years, they referred to him as gloomy, withdrawn, and hyper-focused or lacking motivation to paint.
In adulthood, van Gogh led a tumultuous life, which one of his physicians described as ‘a simple artist’s bout of craziness’, while another described it as ‘attacks of epilepsy, separated by long intervals’.
Van Gogh himself described feelings of being ‘bound hand and foot, lying in a deep, dark pit, powerless to do anything’ and reported that sometimes he felt fear- and sorrowful, which ‘cannot but make one agitated and nervous in speech and manner’.
Moreover, he mentions that he does not enjoy company, and that dealing with people, talking to them, is often painful and difficult. He also wrote that he ‘is overcome by a ‘feeling of great anxiety, dejection and even despair’.
This is often followed by complaints of procrastination and hesitancy in everything, followed a few months later by reports that he is working from early till late and being ‘absorbed in the moment’.
In December 1888 – two years before he shot himself, he famously cut off his left ear, which his then physician concluded was the result of ‘transient over-excitement’ caused by his lifestyle of too much alcohol, coffee, tobacco, and poor food.
Following this dramatic event, van Gogh was transferred to an asylum in May 1889. During his time in the asylum, it was noted that he appeared to have no will and hardly any desires. The physician in charge of his treatment described the ear incident as ‘an attack of acute mania with generalised delirium’.
As alluded to above, van Gogh described feelings of being ‘bound hand and foot, lying in a deep, dark pit, powerless to do anything’, while his family called him melancholic from a young age. According to the authors of the study, van Gogh often showed mood swings.
His brother, Theo, described van Gogh as having two conflicting personalities: one a gifted, sensitive, and gentle person, the other as self-loving and unfeeling. Theo also reported that van Gogh would often complain of procrastination and other periods of working day and night and hardly sleeping.
Comorbidities associated with BMD
Psychiatric and medical comorbidities in patients with BMD have received increasing attention in recent years. It is extremely important that comorbidities are taken into consideration when treating a patient with BMD because has been postulated that specific bipolar comorbidity associations may have an impact on the treatment of BMD.
High prevalence rates of certain psychiatric comorbidities among patients with BPD have been reported, including personality disorders (9%-89%), alcohol and substance abuse (17%-60.7%), and anxiety disorders (25.2%-30.6%).
In addition, studies have found that patients with BMD are at an increased risk of epilepsy compared to controls. Furthermore, Smith et al found that the rate of epilepsy is higher in patients with BMD compared to the general population.
According to Nolen et al, Van Gogh showed identity and attachment problems and/or personality problems, more specifically with borderline features. Depending on the evaluation whether or not there was an enduring pattern with impairment, he had a personality disorder or traits thereof.
In addition, there appeared to be an evolving mood disorder, more particularly recurrent depressive episodes probably in the course of a BMD. As of the end of 1888, his mental and somatic health deteriorated, preceded by an increase of alcohol consumption combined with malnutrition,
resulting in the ear incident. Another theoretical explanation of (part of) the symptomatology is focal (temporal lobe) epilepsy, either as co-morbidity or as a differential diagnosis.
Could van Gogh have been treated successfully?
Recent guidelines recommend various second generation antipsychotics (SGAs), lithium (mood stabiliser), and valproate (anticonvulsant) as first-line monotherapy for adults with acute mania.
Locally, the CMS recommends the use of the following agents:
- Anti-manic agent
- Bipolar depression agent
- Maintenance agent.
Anti-manic agents
Anti-manic agents include anticonvulsants (eg sodium valproate, carbamazepine, and lamotrigine), lithium and antipsychotics. Based on randomised clinical trials, lithium occupies a particularly important role in the prevention of relapse to mania and depression.
Valproate and lithium are used in the manic episode as monotherapy or in combination with atypical antipsychotics. Valproate should be used with extreme caution in women of childbearing age due to the risk of foetal malformations and adverse neurodevelopmental outcomes after any exposure in pregnancy. Lamotrigine is used in the maintenance mainly for the prevention of depressive episodes. There is no consensus of the role of carbamazepine, it is however listed as a second line maintenance agent in the South African Society of Psychiatrists guidelines.
Antipsychotics
Antipsychotics are classified as typical (first generation antipsychotics) or atypical (second generation antipsychotics). Atypical antipsychotics are the newer drugs which are generally well tolerated with less side effects when compared to the older drugs. Medicines in this class are recommended as first-line agents.
Typical antipsychotics are the older drugs with generally more serious side effects and are recommended as second-line agents. Lamotrigine, valproate, and lithium are also recommended in the depressive phase of BMD. Atypical antipsychotics (eg) quetiapine and olanzapine are recommended as PMB level of care.
Bipolar depression agents
Antidepressants are the most commonly prescribed drug class for treating depression. The benefits of conventional antidepressants such as the tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin and noradrenaline reuptake inhibitors (SNRIs) in the treatment of BMD is currently unclear.
If a conventional antidepressant is employed for BMD depression, it should be concurrently administered with an anti-manic maintenance agent to diminish the possibility of switching.
SSRIs (eg fluoxetine, citalopram, escitalopram) are recommended as first-line antidepressants in combination with mood stabilisers.
Maintenance therapy
There is limited evidence for combining treatments hence monotherapy is preferred. Kishi et al (2021) conducted a systematic review and network meta-analysis for 21 outcomes related to the efficacy, acceptability, tolerability, and safety of 23 drugs and placebo in the treatment of adults with acute BMD mania.
Table 3: Agents included in the study were:
Aripiprazole Asenapine Brexpiprazole Carbamazepine Cariprazine Chlorpromazine Endoxifen Eslicarbazepine Haloperidol Lamotrigine Licarbazepine Lithium
Olanzapine Oxcarbazepine Paliperidone Quetiapine Risperidone Tamoxifen Topiramate Valnoctamide Valproate Verapamil Ziprasidone Placebo
Aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone showed a better response to treatment than the placebo. The response rate (RR) ranged from 7.461 for tamoxifen to 1.281 for asenapine.
Aripiprazole, cariprazine, and quetiapine outperformed eslicarbazepine, licarbazepine, and topiramate. Asenapine, lamotrigine, paliperidone, and ziprasidone outperformed topiramate.
Carbamazepine outperformed asenapine, endoxifen, eslicarbazepine, lamotrigine, licarbazepine, and topiramate. Haloperidol, olanzapine, and risperidone outperformed asenapine, eslicarbazepine, licarbazepine, and topiramate.
Lithium and valproate outperformed eslicarbazepine and topiramate and tamoxifen outperformed all active-drugs other than carbamazepine and verapamil.
Compared with the placebo, aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation ranged from 0.647 for olanzapine to 0.840 for aripiprazole, whereas topiramate had higher all-cause discontinuation.
Aripiprazole, carbamazepine, haloperidol, valproate, and ziprasidone outperformed topiramate and valnoctamide. Olanzapine outperformed aripiprazole, asenapine, brexpiprazole, cariprazine, haloperidol, lamotrigine, licarbazepine, lithium, topiramate, valnoctamide, valproate, verapamil, and ziprasidone.
Paliperidone and risperidone outperformed topiramate, valnoctamide, and verapamil and quetiapine outperformed lithium, topiramate, valnoctamide, and verapamil.
In term of mania rating score, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone showed better improvement of the mania rating scale score compared to placebo. The SMD ranged from −1.806 for tamoxifen to −0.216 for valproate.
Aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy, with the RR ranging from 0.349 for paliperidone to 0.716 for lithium compared to placebo.
Aripiprazole, asenapine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, and tamoxifen outperformed the placebo for clinical remission. The RR ranged from 8.441 for tamoxifen to 1.259 for lithium.
Compared with the placebo, aripiprazole, cariprazine, haloperidol, olanzapine, quetiapine, risperidone, tamoxifen, and ziprasidone showed better improvement of psychotic symptoms. The SMD ranged from −1.640 for tamoxifen to −0.266 for aripiprazole.
Compared with the placebo, asenapine (RR = 1.896), haloperidol (RR = 1.867), and lithium (RR = 1.791 had higher discontinuation due to adverse events, while olanzapine had lower discontinuation due to withdrawal consent (RR = 0.643).
No drug was associated with the incidence of depression compared with the placebo. In addition, compared with the placebo, olanzapine (RR = 0.881) and quetiapine (RR = 0.767) were associated with a lower frequency of anxiolytic use. Aripiprazole, cariprazine, haloperidol, paliperidone, risperidone, and ziprasidone were associated with a higher frequency of anticholinergic use (RR ranged from 2.374 for paliperidone to 6.299 for haloperidol.
Aripiprazole, brexpiprazole, cariprazine, haloperidol, paliperidone, risperidone, and ziprasidone were associated with a higher incidence of akathisia (RR ranged from 2.586 for paliperidone to 5.579 for haloperidol.
Aripiprazole, asenapine, cariprazine, haloperidol, lithium, olanzapine, risperidone, and ziprasidone were associated with a higher incidence of extrapyramidal symptoms (RR ranged from 1.817 for olanzapine to 5.337 for haloperidol).
Aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone were associated with a higher incidence of somnolence (RR ranged from 1.609 for lithium to 5.158 for cariprazine.
Asenapine, carbamazepine, haloperidol, olanzapine, quetiapine, valproate, and ziprasidone were associated with a higher incidence of dizziness (RR ranged from 2.037 for valproate to 3.552 for carbamazepine.
Carbamazepine (RR = 4.079), olanzapine (RR = 3.758), and quetiapine (RR = 3.630) were associated with a higher incidence of dry mouth. Aripiprazole, cariprazine, olanzapine, and quetiapine were associated with a higher incidence of constipation (RR ranged from 1.735 for aripiprazole to 2.866 for quetiapine, and asenapine, olanzapine, paliperidone, quetiapine, valproate, and ziprasidone were associated with a higher incidence of weight gain (RR ranged from 2.928 for ziprasidone to 8.180 for olanzapine.
Compared with the placebo, quetiapine was associated with a lower incidence of nausea (RR = 0.313), whereas aripiprazole, carbamazepine, cariprazine, lithium, risperidone, and valproate were associated with a higher incidence of nausea. The RR ranged from 1.558 for aripiprazole to 4.664 for risperidone. There were no significant differences in the incidence of headache and diarrhoea between each drug and the placebo.
The authors concluded that aripiprazole, olanzapine, quetiapine, and risperidone outperformed placebo in terms of efficacy, acceptability response to treatment, all-cause discontinuation (primary outcomes), improvement of mania symptoms and discontinuation due to inefficacy (secondary outcomes).
These SGAs also outperformed the placebo in terms of clinical remission and improvement of psychotic symptoms. Therefore, they appear to have a better balance of efficacy and acceptability in the treatment of acute mania than that of other drugs.
Non-pharmacological management in and out-of-hospital
There is strong evidence for non-pharmacological management to compliment pharmacotherapy in the holistic management of BMD.
These interventions should include the entire multidisciplinary team. Psychosocial modalities, including psychoeducation and behaviour change, should be integrated into the pharmacotherapy treatment regimen. Adjunctive psychosocial therapies should also be considered early in the course of illness to improve medication adherence, identify prodromes of relapse, decrease residual symptoms.
Psychoeducation focusing on recognition of early warning signs of relapse is an effective adjunct to medication management and should be offered to all patients with BMD.
More intensive psychotherapies (cognitive-behavioural therapy, family focused therapy, interpersonal and social rhythm therapy) have also demonstrated benefit as adjuncts to improve both symptoms and function and should be considered.
REFERENCES:
- Council for Medical Schemes. PMB definition guidelines for bipolar mood disorder Version 1: 30.09.2020. https://www.randwater.co.za/RW%20Medical%20AID%20Communique/CMS/PMB_Definition_Guideline_for_Bipolar_Mood_Disorder_v1.pdf
- Dome P, Rihmer Z and Gonda X. Suicide Risk in Bipolar Disorder: A Brief Review. Medicina (Kaunas), 2019
- Forty L, Ulanova A, Jones L, et al. Comorbid medical illness in bipolar disorder. BJPsych, 2018.
- Guo JJ, Patel NC, Li H and Keck PE. Prevalence of Treated Bipolar Disorders and Associated Comorbidities in Managed Care and Medicaid Populations. AHDB, 2010.
- Nolen WA, van Meekeren E, Voskuil P, and van Tilburg W. New vision on the mental problems of Vincent van Gogh; results from a bottom‑up approach using (semi‑)structured diagnostic interviews. Int J Bipolar Disord, 2020.
- Kishi T, Ikuta T, Matsuda Y, et al. Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials. Molecular Psychiatry, 2021.
