Visual Hallucinations in Parkinson’s Disease

Visual Hallucinations in Parkinson’s disease

Parkinson’s disease has gotten a lot of media attention in the past year. Michael J. Fox has brought remarkable attention and funding to the disease since his diagnosis in 1992. He sparked a lot of conversation regarding treatment and research about Parkinson’s in 2013 when he starred in the NBC show The Michael J Fox Show. 2014 however brought new light to Parkinson’s disease in the media when it was made public that prior to his suicide, Robin Williams was diagnosed to be in the early stages of Parkinson’s disease. Unfortunately since then there has not been much light shed publically about the treatment of psychiatric illnesses in patients already or newly diagnosed with Parkinson’s disease.

Parkinson’s disease is a degenerative disease that’s primary effect is on the motor function of the patient. This does not mean that symptoms are limited to motor function, both emotional and social functioning can be markedly impaired as well. Recently literature has started suggesting that the non-motor symptoms associated with Parkinson’s disease are more debilitating than the motor symptoms. Psychiatric care within Parkinson’s disease encompasses emotional disturbances such as anxiety and depression, psychosis, and sleep disturbances. With all psychiatric care behavioral modifications should be part of a well-rounded treatment plan, however for this post the focus will be pharmacologic management of symptoms with the neurobiology of the symptoms specifically taken into account. In a literature review done by Dr. Rosa Quelhas in 2013, it was shown that there are numerous studies showing the effectiveness of medications on the differing psychiatric concerns for each patient. Anxiety, depression, sleep, and psychosis are all approached slightly differently in Parkinson’s disease because of the neurobiological differences in the Parkinsonian brain.

According to Quelhas psychosis is one of the most common and well-studied psychiatric concerns in Parkinson’s disease. Psychosis could be attributed to the long-term use of anti-Parkinsonian medications, older age of patients, longer disease duration, comorbid depression, and/or comorbid dementia (Quelhas, 2013). Psychotic symptoms in Parkinson’s disease are typically visual hallucinations, many times which are not emotionally driven. Kiferle et al. in their article about visual hallucinations in Parkinson’s disease patients found through SPECT studies numerous areas of the brain were activated. These areas of the brain included the posterior cortical areas which are involved in visual perceptions as well as significantly less activation in numerous regions of the frontal area of the brain (Kiferle, 2014). These frontal areas of the brain where there is less activation in patients suffering from Parkinson’s are the areas that have been associated with attention- meaning that decreased activation in these areas might put patients at an increased risk for visual hallucinations. The basal ganglia’s involvement in the development of visual hallucinations has also been the subject of several studies. This is probably because of the interactions between the basal ganglia and the fronto-striatal circuits connecting it to the frontal areas. fMRI studies have shown that patients with visual hallucinations had increased caudate nucleus uptake reduction, again pointing to dopamine in the Parkinsonian brain.

Treatment of psychiatric symptoms in Parkinson’s has to take into account the neurobiology of Parkinson’s disease and the mechanism of action of the medications. Something that also needs to be taken into account are the motor symptoms that the patient most likely already has due to Parkinson’s and being careful to not exacerbate those symptoms. This is readily taken into account when considering first-generation antipsychotics in Parkinson’s disease. It has been shown that typically patients cannot tolerate first-generation antipsychotics because high doses tends to produce extrapyramidal symptoms while lose dose first-generation antipsychotics tend to have significant side effects that patients find intolerable.

Clozapine, a second-generation antipsychotic, has been shown in numerous drug trials and studies to be an effective agent in treating the psychotic symptoms in patients with Parkinson’s disease without exacerbating motor symptoms. It has been claimed to be the “gold standard antipsychotic treatment” (Quelhas, 2013) for psychotic symptoms. According to the review done by Quelhas, clozapine has also been shown in several studies to have a benefit in improving other symptomatology in Parkinson’s disease such as akathesia, dystonia, and neurogenic bladder. The efficacy of clozapine in Parkinson’s disease has been of great interest in the past couple years because while it is a non-selective antagonist of both serotonergic and dopaminergic receptors its exact mechanisms are not currently fully understood. Clozapine has been shown in studies to have an anti-tremor property as well, which makes it an excellent choice for the treatment of psychotic symptoms because it has been shown to cause reductions in the prescribing cascade- meaning that the number of medications prescribed to treat the side effects of another prescribed medications is reduced. This both could streamline a patient’s medication regimen as well as promote medication regimen adherence. Fewer individual medications and a lower side effect profile of all medications has been shown to increase patient satisfaction with their care (Toure et al, 2006).

Mirtazapine was shown to have specific efficacy in the treatment of visual hallucinations in a case report published by Tagai et al. in 2013. The article discussed the criteria for psychosis within the population of patients suffering from psychosis, including visual hallucinations. Tagai et al recognized that while the underlying neural biology of psychotic symptoms in Parkinson’s disease is still largely unclear, mirtazapine appeared to target both the serotonin and acetylcholine receptors that play an emergence in the visual hallucinations.





Kiferle, L., Ceravolo, R., Giuntini, M., Linsalata, G., Puccini, G., Volterrani, D., & Bonuccelli, U. (Jul 2014). Caudate dopaminergic denervation and visual hallucinations: Evidence from a 2I-FP-CIT SPECT study. Parkinsonism & Related Disorders, 20, 761-765. doi:

Quelhas, R. (2013). Psychiatric Care in Parkinson’s Disease. Journal of Psychiatric Practice, 118-141.

Tagai, K., Nagata, T., Shinagawa, S., Tsuno, N., Ozone, M., & Nakayama, K. (Jun 2013). Mirtazapine improves visual hallucinations in parkinson’s disease: A case report. Psychogeriatrics, 13, 103-107. doi:

Toure JT, Brandt NJ, Limacangco MR, et al. Impact of second-generation antipsyhotics on the use of antiparkinson agents in nursing homes and assisted-living facilities. American Journal of Geriatric Pharmacotherapy. 2006; 4:25-35

Wikipedia . (2015, March). Michael J. Fox. Retrieved from Wikipedia:

A Look at OCD

When we think of obsessive-compulsive disorder (OCD), we think of a person constantly washing his or her hands or someone who repeatedly checks to make sure the stove is off. However, there are actually different types of OCD. Besides fear of contamination, the other types include having taboo thoughts and fear of carrying them out (this includes fear of harming others), fear of general harm, and need for organization/symmetry (Roth, 2015).

The root of the behaviors is doubt. Specifically, those with OCD have trouble distinguishing between probable and highly unlikely events, and therefore experience undue anxiety related to their irrational thoughts (also known as obsessions). In order to mitigate the anxiety, and in some instances, to prevent a bad event from occurring, they perform rituals (also known as compulsions). They are cognitively aware that the obsessions and compulsions are irrational but are unable to control the anxiety associated with the intrusive thoughts (NAMI, 2015).

Cortico-striatal-thalamic-cortical circuit (CSTC) in OCD

Neuroimaging studies have pinpointed three brain structures involved in OCD: the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC), and the basal ganglia. In general, studies have shown that these areas are more activated in OCD as compared with healthy controls. Furthermore, these areas also become increasingly activated when experiencing obsessive thoughts. Successful treatment decreased activity in those areas (Whiteside, 2004). The rationale for why these areas are hyperactivated points to an imbalance in the pathways through the basal ganglia when messages are relayed via the CSTC circuit. This circuit involves the cerebral cortex, basal ganglia (in particular, the caudate and putamen – together called the striatum), and the thalamus. The loop starts with the cortex, which transmits messages to the basal ganglia, which in turn sends a signal to the thalamus, which then loops back to the cortex. In normal brains, there is a balance between excitatory and inhibitory pathways in the circuit, but in OCD patients, the excitatory pathway dominates (Saxena & Rauch, 2000). This explains the hyperactivation seen in functional imaging studies.

Given these findings, one might wonder whether the hyper activation is a result of OCD traits or vice versa. Recent studies have elucidated the cause and effect relationship between hyper activation of the CSTC circuit and OCD traits. In one study, after light sensitive genes were injected into the orbitofrontal cortex of mice, optical fiber was inserted in the brain and attached to a cable that aims pulses of laser light at the ventromedial striatum (part of the caudate and putamen). This, in turn, activates the connections between the frontal cortex and ventromedial striatum. After repeated stimulation of the circuit, the mice began exhibiting OCD-like symptoms in the form of excessive grooming. After the light stimulation ceased, the excessive grooming activity gradually returned to normal (Ahmari et al., 2013). The results of this study give evidence for circuit dysregulation as a contributing factor to OCD development.

Glutamate in OCD

In the past ten years, there has been increasing attention paid to the neurotransmitter glutamate. Our current first line OCD treatments target serotonin and norepinephrine, but one-third of patients undergoing these treatments still experience significant symptoms. It turns out that glutamate plays an important role in OCD symptom manifestation. Abnormally high levels of glutamate have been associated with OCD symptoms. In a study examining cerebrospinal fluid (CSF), it was found that those with untreated OCD possessed higher levels of glutamate in the CSF as compared with healthy controls (Bhattacharyya et al., 2009). Given these findings, one might hypothesize that medications with the ability to reduce glutamate may have a beneficial effect in reducing OCD symptoms. Preliminary research has confirmed this hypothesis, although evidence is not yet conclusive. One NMDA antagonist, Ketamine, has been in the spotlight lately as a possible new treatment to depression. Unlike selective-serotonin reuptake inhibitors (SSRIs), which start to produce effects in weeks, Ketamine produces exceptionally fast results (McGirr et al., 2014). Ketamine appears to produce similarly fast acting results in OCD as it does in depression. What’s more, in a recent randomized controlled trial, the immediate symptom improvements were seen in all participants and lasted up to one week in some participants (Rodriguez et al., 2013). Although these findings are promising, there exist potential drawbacks as well. First of all, it needs to be administrated intravenously, which renders it infeasible for long-term and widespread use. Secondly, Ketamine is also used as a club drug and possesses abuse and addictive potential. Lastly, its infusion causes hefty side effects such as psychotic symptoms, feelings of dissociation, and manic symptoms, and the effects of long-term use have not been established.

Research has presented a constellation of structural, genetic and neurobiological factors that contribute to the pathogenesis of OCD, albeit many connecting pieces are still unknown. For those suffering with treatment refractory OCD, there is hope in the new advances and treatment options that have emerged in the recent years. It is my hope that eventually every individual suffering from this debilitating disorder will achieve relief.


Ahmari, S. E., Spellman, T., Douglass, N. L., Kheirbek, M. A., Simpson, H. B., Deisseroth, K., … & Hen, R. (2013). Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science, 340(6137), 1234-1239.

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM-5. Washington, D.C: American Psychiatric Association.

Bhattacharyya S, Khanna S, Chakrabarty K, Mahadevan A, Christopher R, Shankar SK (2009). Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder.

Maia, T. V., Cooney, R. E., & Peterson, B. S. (2008). The neural bases of obsessive-compulsive disorder in children and adults. Development and Psychopathology, 1251-1283.

McGirr, A., Berlim, M. T., Bond, D. J., Fleck, M. P., Yatham, L. N., & Lam, R. W. (2014). A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychological medicine, 1-12.

NAMI (2015). Obsessive-Compulsive Disorder. Retrieved February 23, 2015, from

Pittenger C, Bloch MH, Williams K (2011). Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment. Pharmacol Ther 132: 314–332

Rodriguez, C. I., Kegeles, L. S., Levinson, A., Feng, T., Marcus, S. M., Vermes, D., … & Simpson, H. B. (2013). Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept.Neuropsychopharmacology, 38(12), 2475-2483.

Roth, M. (2015, February 1). Severe OCD has significant consequences. Retrieved February 23, 2015, from

Saxena, S., & Rauch, S. L. (2000). Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatric Clinics of North America, 23, 563-586.

Whiteside, S.P., Port, J.D., & Abramowitz, J.S. (2004). A meta-analysis of functional neuroimaging in obsessive-compulsive disorder. Psychiatry Research, 132, 69-79.