Varun Bisessar
Michael Grove
ENGL21003
12/19/2018
Bipolar-OCD: Clinical complications and understudied treatments

Patients who suffer from bipolar-OCD are often forced to experience hours of psychotherapy because of a lack of diverse treatment methods due to limited treatment studies. Disparities between the discussion of bipolar-OCD in India, China, Sweden, and Switzerland compared to the United States becomes evident when patients are faced with the inconvenience of SSRIs and psychotherapy. In the United States alone there are three million bipolar cases and two hundred thousand obsessive compulsive cases documented annually. Recent evidence indicates that SSRIs and mood stabilization techniques are relatively effective treatments, however, the use of medication has not been approved because of lackluster evidence and limited case reports. The use of other conventional pharmacological agents and psychotherapy for treating comorbid OCD in BD must be researched in the United States to eliminate the clinical complications produced by studies conducted in primarily India and China.

“In 1995, a study conducted in Germany revealed that patients with a primary diagnosis of bipolar disorder had experienced other mental disorders, prevalent were symptoms of OCD.” (Shi, 2015). The limitations of bipolar-OCD research have partly decreased because of recent publications. Previously vast publications had not specified whether the groups they studied were experiencing manic episodes during the study time frame. Manic episodes increase the occurrence of obsessive-compulsive symptoms which could have resulted in a wrongful diagnosis of patients. Also, as attention towards these patients has grown, the research produced must also grow. Many of these studies are conducted in India and China, the scale size of the research groups has limited the number of patients that can be studied. The studies currently available have not declared a funding source which may reason the limitations of data available.

The lack of a funding source limits the amount of the patients studied, this becomes an issue because of the locations where the current studies were conducted. Cultural homogeneity is one of the factors that contribute to the difficulty in analyzing data produced by studies in China and India. Cultural homogenous locations such as China removes the data factor of genetic diversity which may account for biased results in a publication. Conducting a study to test the best methods of treatment for bipolar-OCD in the United States would be more challenging because scientists would have to account for different genetic variables. Currently, patients experiencing symptoms of bipolar-OCD are being treated with methods adopted from Indian and Chinese publications. Although the use of SSRIs and psychotherapy can manage the symptoms, there is a severe level of inconvenience for those who SSRIs are ineffective for. Efforts to study the effects of medications used for the separate disorders can help determine if the development of medication for bipolar-OCD is viable.

“Small sample size and enrollment of subjects mainly from BD-OCD outpatient units may limit the generalizability of these results.” (Amerio, 2016). Amerio references separate studies, one conducted in India and another in China, the sample sizes of those studies limited the generalizability of the successful treatments which meant that the results produced by the sample subjects were not suitable to be used for a general treatment method. The systematic review that Amerio and his team produced stressed the importance of control groups and larger studies. Many of these results rely heavily on data produced by a set of countries in relatively close proximity.

The concern about control groups in locations like China and India results from a lack of biodiversity. “Potential confounding factors in these studies include demographic and historical illness variables, which often were not appropriately analyzed through multivariate modeling, the tests used may be insensitive to potential publication bias.” (Amerio, 2016). The demographic factor that Amerio mentions effects the methods used for treatment because the treatments currently employed by physicians in India and China include the use of SSRIs and a combination of psychotherapy techniques. These psychotherapy techniques along with SSRIs are costly and may not be as effective when transiting this treatment method outside of the region that the method originally experienced success.

In the United States alone there are more than three million bipolar disorder cases and more than two hundred thousand obsessive-compulsive disorders cases documented. However, there have only been two studies in the United States regarding how to properly diagnose bipolar-OCD and there have been no studies conducted regarding the treatment of bipolar-OCD. Therefore, it is imperative that before adopting the use of psychotherapy and SSRIs from China and India, the use of other conventional pharmacological agents along with psychotherapy and SSRIs for treating bipolar-OCD must be researched in the United States to eliminate the clinical complications produced by studies conducted in India and China. Mock studies have been created by psychologists prominent in the field of bipolar-OCD to prevent negative impacts on patients if the treatment methods adopted from China and India do not share the same success.

However, a study has not been carried out as yet. As a result, “Polypharmacy and poor treatment response are also documented in BD-OCD comorbidity.” (Kazhungil, 2016). This becomes an issue for patients in the United States because for the patients that psychotherapy and SSRIs are not effective there are no viable treatments. Regardless, for those patients that a combination of SSRIs and psychotherapy are effective for, psychotherapy remains an inconvenient method of treatment because it is very time-consuming. If it is possible that with studies and patient testing that an effective treatment can be developed, then what are we waiting for? Pure BD and OCD are manageable with medication, however, while bipolar-OCD prevalence grows the treatment response mechanisms remains stagnant. “The presence of OCD poses a huge impact on morbidity of patients with BD. BD when comorbid with OCD has been associated with greater disability and poorer quality of life, poor functioning, and higher unemployment in comparison to “pure” OCD or “pure” BD.” (Kazhungil, 2016).

Kazhungil and his group have studied BD and OCD in their pure forms, they have used the data collected to create a mock study that can be conducted on patients with bipolar-OCD in the United States. One of the strengths of Kazhungil studies is the basis to which he wants the study to begin, he suggests that the study should begin with analyzing the neurological aspects of bipolar-OCD patients in order to test the effectiveness of pharmacological treatments. He admits, monitoring the neurochemical activity of the brain could reveal any changes in mood stability. The neurotransmitters the model studies are focused on are serotonin, glutamate, and dopamine. “It can be presumed that BD-OCD may have less chance of mood instability when selective SRI (SSRI) is used to treat OCD in BD.” (Kazhungil, 2016). Gathered from the treatment studies Kazhungil and his team conducted in India and China, SSRIs have been proven to lower the chance of mood instability, however, it has not been effective for everyone.

Considering the demographics of Kazhungil and his team, Cederlöf and his team conducted a treatment study in Sweden and revealed that SSRIs were not as effective regarding the mood stability of the patients. They found that the data was, “Consistent with the known association between antidepressant use and switch to mania in patients with bipolar disorder.” (Cederlöf, 2015). Moving forward targeting dopamine and glutamate instead of serotonin may be helpful. Currently, no country has focused on a glutamate or dopamine hypothesis regarding bipolar-OCD. The resources are available in the United States and the abundance of these disorders can assist in organizing large groups of patients to study. Bipolar-OCD treatment has brought about clinical complications that will continue to expand as the abundance of the comorbid conditions rises. Using the model studies created by Kazhungil and his group along with the Swedish study by Cederlöf and his group, a study can be produced and conducted to undermine the shortcomings of Chinese and Indian studies.

There are no justifications as to why these sorts of studies continue to lack in the United States. Many studies have been conducted in India and China and prominent psychologists such as Amerio have declared that the demographical factors of the locations the studies were conducted to limit the possibility of generalizability of the treatment methods. Other psychologists in the field argue against conducting further studies in the United States. “Among the antipsychotics, olanzapine has been found to be less effective in the treatment of BPAD-OCD. However, this was not the case in our patient who responded well to olanzapine leading to complete remission of mania.” (Chandran, 2017). The arguments that psychologists such as Chandran make is most of the answers surrounding bipolar-OCD are available. Chandran’s study was conducted in India and found one patient who had erased all symptoms of OCD while taking olanzapine. Chandran does not account for demographic effects that may change the results of this study is conducted elsewhere, however, he does acknowledge that in broader studies “atypical antipsychotics (such as clozapine and olanzapine) have been known to cause/worsen the OC symptoms” (Chandran, 2017). Ultimately Chandran’s antipsychotic hypothesis will be refuted by this proposal as a whole.

Although SSRIs and Psychotherapy have helped many patients, there are many patients in desperate need of help. The model studies from Kazhungil and Cederlöf will guide the following study that should be conducted in the United States. The study should begin with the collection of data from psychologists throughout the United States to gather cases of bipolar-OCD patients to begin a selection process for studies. One of the major shortcomings of many Indian and Chinese studies was the sample sizes. The selection process for the study should break down to two selection groups, one selection group of patients diagnosed with bipolar disorder before being diagnosed with obsessive-compulsive disorder and another group diagnosed with obsessive-compulsive disorder before being diagnosed with bipolar disorder. After reviewing many of the Indian and Chinese studies there were no disclaimers that mentioned the primary versus secondary diagnoses of the patients.

Possibly the primary versus secondary diagnosis could impact the methods of treatment suited for that patient group. Therefore, the study will be conducted separately for each group. Previously Amerio has been critical about studies that shared small sample sizes and were not able to include a control group. The control group used for this study will include pure BD and OCD patients because the focus of the study is finding a treatment that will be effective for bipolar-OCD patients considering their effectiveness for the pure disorders. Similar to the methods that Indian and Chinese studies used to find that SSRIs and psychotherapy were a possible treatment method after many believed there were no treatment methods at all for bipolar-OCD patients.

Swedish studies were similar to Indian and Chinese studies in the sense that they had no control group. “The biggest limitation of the current study may be that OCD is underrepresented in the Swedish national patient register compared with the other disorders under study. This is largely due to the fact that OCD rarely requires hospitalization.” (Cederlöf, 2015). Cederlöf exposes one of the shortcomings of the study groups in Sweden as the groups did not include a control group because the hospitals have limited or no record of OCD patients. Therefore, pure OCD patients will act as a control group for the study conducted in the United States.

Many Indian and Chinese studies did not acknowledge the neurological aspects of bipolar-OCD. The neurological aspects of bipolar-OCD as explained by Kazhungil break down to the neurotransmitter’s serotonin, glutamate, and dopamine. In the mock studies that Kazhungil and his team created, they suggested targeting a different neurotransmitter. “Studies of pharmacological interventions targeting glutamate have been in progress, both in BD and OCD.” (Kazhungil, 2016). From studies of glutamate in pure BD and OCD, it was found that agents such as Lamotrigine, Riluzole, Memantine, N-Acetylcysteine, and Topiramate have all been in some form effective when treating either pure BD or OCD. Therefore, using these agents in a multisectoral study may reveal some uses of glutamate in the treatment of bipolar-OCD. “Hence, we may observe that glutamatergic drugs may be of promising effects in BD-OCD comorbidity.” (Kazhungil, 2016).

Dopamine is another mechanism closely related to the characteristics of mania from BD. Mania is often exacerbated when SSRIs are used to treat OCD because of an increase in the functional level of dopamine in the patient. Reasoning as to why some patients may be able to take SSRIs is because the SSRIs do not affect their dopamine levels as much. If there was a method to keep dopamine levels low while taking SSRIs then a possible treatment method may evolve. “Valproate has been tested and revealed promising data in a study of BD patients. Valproate decreased dopaminergic function in manic BD patients.” (Kazhungil, 2016). The challenge is presented when combining an SSRI along with Valproate. The “SRI-refractory OCD has additional abnormalities in the dopaminergic function that requires augmentation with dopamine-blocking agents.” (Kazhungil, 2016).

The following study will examine the current methods used to treat bipolar-OCD and weigh their effectiveness compared to experimental methods targeting separate neurotransmitters. Compared to treatments that require psychotherapy, uses of medications to interfere with the behavior of neurotransmitters may develop an accepted treatment. This study will require planning and organization in order to gather bipolar-OCD patient records. It is imperative to group patients by their primary diagnosis because it has been argued by Amerio that, “The patients who are primarily diagnosed with BD only experienced obsessive-compulsive symptoms during manic episodes, making it less likely that (SSRIs) would exacerbate obsessive-compulsive symptoms. However, the second category of patients is diagnosed with primary OCD and a secondary diagnosis of BD with obsessive-compulsive symptoms” (Amerio, 2016). Therefore, this study will be divided into multiple sections.

The first section will test the effectiveness of targeting serotonin, representing the standard treatment of SSRIs and psychotherapy. The second section will test the effectiveness of targeting glutamate with the use of glutamatergic drugs such as Lamotrigine, Riluzole, Memantine, N-Acetylcysteine, and Topiramate, the primary drug used would be decided by the organizers of the study. The third section will test the effectiveness of targeting dopamine with the use of the primary drug of Valproate. It is imperative to group patients by their primary diagnosis because a drug that showed effectiveness for the patient before being diagnosed with a secondary condition may be more effective when tested on those patients after diagnosed with a secondary condition. To avoid biases results groups would be divided half and half, patients who for example experienced success with SSRIs and psychotherapy will be divided with some patients remaining in that group and others moved to another group. This study will have to be conducted possibly over a year or longer in order to gather adequate results and will require replications.

Limitations of this study remain in the organizational aspects as of now, however after this study is conducted limitations may arise in data collection. Other limitations to acknowledge may be some patients of a particular study may be omitted because of negative reactions to medications. Future research and replications along with changes to this study as modeled by Kazhungil and Cederlöf will be necessary to examine the plausibility of the primary study. It is possible that a drug can be created, and the symptoms of bipolar-OCD can be managed. As of now the goals of this study remain on an organization basis, however, the long run goal is to identify the neurotransmitter that should be targeted and finding the right combination of medications to find an alternative treatment method to the currently accepted treatment method in India and China of the use of SSRIs and psychotherapy.

References:
Amerio, A., Stubbs, B., Odone, A., Tonna, M., Marchesi, C., & Nassir Ghaemi, S. (2016). Bipolar I and II Disorders; A Systematic Review and Meta-Analysis on Differences in Comorbid Obsessive-Compulsive Disorder. Iranian journal of psychiatry and behavioral sciences, 10(3).
Chandran, N., Parmar, A., & Deb, K. S. (2017). A Rare Presentation of a Case of Obsessive-compulsive Disorder Comorbid with Bipolar Affective Disorder. Indian journal of psychological medicine, 39(6), 794-796.
Kazhungil F, Mohandas E. (2016). Management of obsessive-compulsive disorder comorbid with bipolar disorder. Indian J Psychiatry, 58(3), 259-269.
Martin Cederlöf, Paul Lichtenstein, Henrik Larsson, Marcus Boman, Christian Rück, Mikael Landén, David Mataix-Cols. (2015). Obsessive-Compulsive Disorder, Psychosis, and Bipolarity: A Longitudinal Cohort and Multigenerational Family Study, Schizophrenia Bulletin, 41(5), 1076–1083.
Shi S. (2015). Obsessive compulsive symptoms in bipolar disorder patients: a comorbid disorder or a subtype of bipolar disorder. Shanghai archives of psychiatry, 27(4), 249-51.