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-HT2A
receptors, and agonistic activity at 5-HT1A
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.
- 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.