Incontinence and mood disorder: is there an association?

Abstract

A variety of psychiatric disorders including depression have been reported in patients suffering from incontinence. It is uncertain if the association between incontinence and depression is causal or is related to a third common factor. We report the case of a 48-year-old man who presented with incontinence of urine and faeces along with a severe depressive episode. No organic cause could be identified for the incontinence. The depressive symptoms as well as the incontinence resolved with treatment with reboxetine and aripiprazole. However, the patient developed a manic episode. This case supports the hypothesis that incontinence and depression may share a common pathogenesis. The authors review the literature to investigate this linkage. The combination of aripiprazole and reboxetine should be used cautiously when treating first episode depression as it can induce a manic switch. Previous reports of manic switch with aripiprazole and reboxetine are reviewed.

Background

Incontinence is generally considered to have an organic origin. However, in a significant percentage of individuals with urinary and/or faecal incontinence no definite structural or functional pathology can be identified.^1,2 A literature search on PubMed using the keywords depression and incontinence revealed a number of studies published in various non-psychiatric medical journals. These included prospective or cross-sectional studies and postal surveys; most reported that female patients with urinary incontinence experience a variety of co-morbid psychiatric disorders, the most common being depression.^3–8 A recent longitudinal study on a cohort of 5820 women concluded that major depression predicted onset of urinary incontinence.⁹ Surprisingly, no published literature was found in psychiatry journals reporting comorbid incontinence with psychiatric disorders except for one case report.¹⁰ This was a case of major depression complicated by bilateral foot drop and double incontinence, which was successfully treated with electroconvulsive therapy with reversal of all the symptoms.

It is unclear if the association between incontinence and depression is causal and, if yes, the direction of causality is uncertain. It is speculated as to whether depression and incontinence are manifestations of a common underlying pathology.

Case presentation

A 48-year-old man presented for the first time with a history of low mood, poor appetite, weight loss, poor sleep, suicidal thoughts, and poor self care for the previous 4 months. He also reported experiencing low energy levels, low confidence and paranoid thoughts that others might harm his family, feeling unsure about the future and feeling helpless. He needed admission to a psychiatric inpatient unit for risks of suicide and self neglect. The patient had received fluoxetine for a month before admission with no benefit.

He was married and lived with his wife and one of five daughters. He was unemployed but had worked as a window cleaner for a few years in the past. He had stopped working 3 years ago after falling from a 10 foot ladder for which he needed admission to the intensive care unit for multiple fractures (of left inferior pubic ramus, left radial neck, left sided rib) and pneumonia. The medical notes confirmed that he had not experienced any head injury or loss of consciousness at the time, and no brain or spinal scan was conducted. Following this accident he experienced flashbacks, symptoms suggestive of anxiety, panic attack, reduced libido, and fleeting suicidal ideas. He started drinking alcohol, gradually increasing to about 10–12 cans of lager (about 20 units) daily. He also smoked 1–2 joints of cannabis over weekends. His wife reported that his life had changed after the accident. He became more socially withdrawn with lack of motivation. There was no history of any mental health problems before the accident. With respect to family history, his brother had committed suicide at the age of 48 and had a diagnosis of paranoid schizophrenia. His developmental history was unremarkable. On physical examination no abnormality was detected.

Investigations

At admission the blood tests showed raised white blood cell count (12.52×10⁹/l) but it returned to normal within a month. The rest of the tests—full blood count, urea, electrolytes, thyroid function test, sugar, glycosylated haemoglobin, lipid profile—were normal. Liver function tests showed increased γ-glutamyl transferase (related to alcohol misuse). Urine microscopy and culture was normal. Computed tomography (CT) scan of the head was reported normal.

Differential diagnosis

At admission, the patient was diagnosed with severe depressive episode with harmful use of alcohol. He was observed to be incontinent of faeces and urine by the nurses on the ward. His wife stated that she had not observed incontinence at home. Therefore, a referral was made to neurology which ruled out any evidence of primary neurological disease. Further investigations were performed including electroencephalogram (EEG), serum copper, creatine kinase, erythrocyte sedimentation rate, autoantibody screen and magnetic resonance imaging (MRI) scan, which were all reported to be normal. The gastroenterologist could detect no specific cause for the faecal incontinence.

Treatment

The patient was commenced on citalopram at 20 mg daily, increased to 40 mg daily after 4 weeks. He was also commenced on thiamine 100 mg daily and vitamin B complex 1 tablet daily. He was not on any other regular prescribed medication. The patient continued to present with low mood, social withdrawal, refusal to eat, psychomotor retardation, and double incontinence about daily, and needed support from the nursing staff to maintain personal hygiene. If prompted, he was able to use the toilet but was unable to explain the reason for incontinence. It did not appear to be urge or stress incontinence. There was no evidence of altered consciousness or disorientation, and his score on the mini mental state examination was 25 out of 30 (losing points on attention and delayed recall). In the absence of any organic cause, it was suspected that incontinence was perhaps a catatonic symptom of depression.¹¹ No other symptoms of catatonia were observed. With no significant improvement with citalopram 40 mg for 4 weeks, aripiprazole was added at a dose of 10 mg daily, increasing to 15 mg in 2 weeks. Duloxetine was considered as an option but could not be used as it was not available on the Trust formulary. The antipsychotic agent aripiprazole was added to augment the effect of antidepressant medication. It would have taken longer for the therapeutic effect to develop if citalopram was changed over to another antidepressant medication. The patient was also expressing paranoid ideas as mentioned above. After 3 weeks on this combination, some improvement was observed but he continued to present low in mood, withdrawn, slow, with poor self care and poverty of speech. The incontinence of urine and faeces was still present but reduced in frequency. Therefore, reboxetine 4 mg twice daily was started, with the citalopram dose halved and stopped after a week. Within a week of initiating reboxetine significant improvement was noted in mood, self-care with remission of incontinence. He was allowed overnight leave home which was followed by discharge from hospital.

The following week he presented with irritable mood, restlessness, high energy levels, talkativeness, extravagance, unable to concentrate and unable to sleep. There was no evidence suggestive of alcohol or drug misuse during this period. The diagnosis was changed to bipolar disorder. Reboxetine was withdrawn immediately and the patient continued on aripiprazole for a week during which no improvement was observed in the manic symptoms. Therefore, aripiprazole was replaced by olanzapine. His mental state started improving within a week and the manic symptoms resolved completely within a month of commencing olanzapine.

Outcome and follow-up

The patient continues to be followed up in the community and is stable on olanzapine 15 mg.

Discussion

The patient presented with depression and double incontinence with no identified organic cause for the incontinence. The incontinence remitted with improvement in mood, after treatment with reboxetine and aripiprazole. This case confirms the hypothesis that depression and incontinence may share a common pathogenesis. We review the literature to investigate the linkage between mood disorder and incontinence. There is one previous case report of major depression accompanied by double incontinence; both the symptoms responded successfully to electroconvulsive therapy.¹⁰

Experimental studies in animals show that lowering the levels of serotonin and norepinephrine (noradrenaline) in the central nervous system leads to depression and urinary frequency and hyperactive bladder.⁸ A similar neurophysiological mechanism at spinal and supraspinal levels has been described to explain the efficacy of duloxetine, a dual serotonin and norepinephrine reuptake inhibitor, in depression, incontinence and neuropathic pain.¹² There are also some reports of efficacy of reboxetine (an antidepressant agent, which is a selective norepinephrine reuptake inhibitor) in children with resistant enuresis.^13,14

Historically, there have been reports of cases presenting with depression or mania associated with incontinence, which were later diagnosed with frontal lobe meningiomas.^15,16 Orbital frontal lobes play a crucial role in controlling emotions and autonomic functions including micturition and defaecation.¹⁷

Micturition is a complex process controlled by various central and peripheral mechanisms. Advances in functional and structural neuroimaging have helped to understand the central control of bladder. The anterior cingulate gyrus and prefrontal region of the frontal lobe have been implicated in the modulation of the central control of bladder, in addition to other subcortical structures.^18–20

Deficits in similar regions of the frontal lobe-anterior cingulate and orbitofrontal cortex have been reported in neuroimaging studies on subjects with mood disorders, including major depressive disorder and bipolar disorder.^21,22 In another study in subjects at high genetic risk of schizophrenia with depressive symptoms, hypofrontality in the form of reduced activation of the dorsolateral prefrontal region has been reported.²³

A recent longitudinal study with a large sample size has reported that women with major depression at baseline were 50% more likely to have urinary incontinence during follow-up than women who were not depressed.⁹

We suspect that our patient might have experienced subtle functional changes to his frontal lobe during the accident 3years ago. This might have contributed to the change in personality described by his wife, following the accident. No brain scan was done at the time of accident; however, CT and MRI scans conducted during the current depressive episode were reported normal. It is hypothesised that the current depressive episode and double incontinence were the manifestations of the underlying brain changes in the frontal lobe which both responded to the treatment with the psychotropic agents.

Another important finding from this case is that the switch from depression to mania occurred within a week of the addition of reboxetine to aripiprazole. However, discontinuation of reboxetine alone did not lead to any improvement in manic symptoms in the following week, requiring replacement of aripiprazole by olanzapine. Manic switch with antidepressant treatment is not a rare occurrence in clinical practice. However, in our patient the switch occurred in spite of the concurrent treatment with aripiprazole, which is known to have antimanic efficacy.²⁴ On literature search, we found one previous report, in which three depressed bipolar patients when treated with reboxetine developed hypomania soon after the addition of the drug to the ongoing regimen with mood stabilisers—lithium and valproate.²⁵ In another open label study of reboxetine in major depressive disorder, one subject was reported to develop a hypomanic switch.²⁶ Therefore, reboxetine needs to be used cautiously in bipolar depression even in the presence of treatment with antimanic agents or mood stabilisers.

Although aripiprazole is efficacious in acute mania,²⁴ there are two previous reports suggesting aripiprazole induced manic episode.^27,28 In our patient, it is possible that the combined effects of reboxetine and aripiprazole led to the manic switch. Reboxetine is a selective norepinephrine reuptake inhibitor. Aripiprazole has combined partial agonistic activity at D₂ receptors, antagonistic activity at 5-HT_2A receptors, and agonistic activity at 5-HT_1A receptors;²⁹ all these can contribute to the development of mania, particularly in the presence of an antidepressant.

It is concluded that double incontinence, associated with depression in the absence of any organic pathology, can remit with treatment of depression. This can be explained by the common pathogenesis of both the conditions. Further research is required to explore the prevalence of urinary, faecal and double incontinence in mood disorders, and to determine if there is any difference in the frequency or severity of incontinence between genders and bipolar and unipolar depression.

The combination of aripiprazole and reboxetine should be used cautiously when treating first episode depression as it can induce a manic switch in a potential bipolar disorder.

Learning points

• Incontinence can be a symptom of depression. It is important to rule out an organic cause.

• There is a need for more systematic research to explore the relationship between depression and incontinence.

• Aripiprazole and reboxetine combination when used to treat a depressive episode can induce a manic switch.