Neuropsychiatric symptoms in Parkinson's Disease

Authors:

Ramsha Tariq,

Danish Batti MD

Introduction

• PD is a neurodegenerative disorder that has historically been seen as a motor disorder

• However, there are significant non-motor symptoms in almost all of the patients with PD

• Including frequent Psychiatric Co-morbidities both in early and late PD

Epidemiology

• More than 10 million people worldwide live with Parkinson’s disease (PD)

• Non-motor neuropsychiatric symptoms in PD are common but under-recognized, often

• Debilitating, with profound impact on
• Social functioning
• Ability to work

• These neuropsychiatric symptoms may include:
• Depression
• Anxiety
• Hallucinations
• Memory problems
• Cognitive impairment/Dementia

• Symptoms are due to both:
• Physical changes to the brain pathology
• Psychological impact of the diagnosis of PD itself

• Depression and anxiety are the most common symptoms;
• Nearly half of people diagnosed with PD suffer one of these mental health issues

Depression

Overview and Diagnosis

• Depression is recognized as a common non-motor symptom of PD

• Patients often underreport their depressive symptoms

• As recommended by International Parkinson and Movement Disorder Society, there are various screening tools used for diagnosing someone who has PD with depression such as
• The Geriatric Depression Scale (GDS)
• Beck Depression Inventory (BDI), Hospital Anxiety and
• Depression Scale (HADS)

Etiology

• Depressive symptoms are more common in PD patients with severe motor symptoms

• Being diagnosed and living with a neurodegenerative condition such as PD can contribute to depressive symptoms

• There is however also a biochemical basis for depression in PD with alteration of serotonin, as well as changes in noradrenaline and acetylcholine neurotransmitters

Treatment

• The specific recommendation of pharmacological therapy depends on severity of symptoms and impact on quality of life

• Like with depression in any chronic state, depression in patients with PD are prescribed
• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin–noradrenaline reuptake inhibitors (SNRIs)
• Tricyclic antidepressants (TCAs) and
• Monoamine oxidase type B (MAO-B) inhibitors

• The best-studied drug for Depression in PD is Paroxetine (SSRI)

• Other commonly used medications by experts are Duloxetine, Citalopram and Escitalopram as well as venlafaxine or mirtazapine especially with concomitant anxiety

Anxiety

Overview and Diagnosis

• Approximately one-third of PD patients experience symptoms of anxiety such as:
• Generalized anxiety disorder (GAD)
• Obsessive-compulsive disorder
• Agoraphobia, panic disorder and
• Social phobia

• Specific symptoms of anxiety in patients with PD include
• Panic attacks
• Excessive worry and
• Increased subjective motor symptoms

• To make diagnosis researchers rely on established criteria such as DSM-IV

• Diagnosis remains challenges include:
• Differentiate symptoms of anxiety from depression (they can occur simultaneously and identification of one should raise suspicion for the other)
• Under-reporting of symptoms by patients
• Under-recognition by clinicians
• Some anxiety symptoms don’t meet the diagnostic criteria threshold

Etiology

• The pathophysiology of anxiety is could be related to neurobiological changes including
• serotonergic and noradrenergic systems which are widely involved in emotion
• those with PD who also score high on anxiety questionnaires were found to have shorter serotonin transporter alleles
• A potential contribution of neuropsychiatric genetics in patients with PD
• psychosocial causes as a result of being burdened with a condition like PD.
• Social anxiety is especially common in
• PD are afraid of being negatively perceived in public which leads to fear of being in public and social withdrawal
• Other patients may fear for their future and the progression of their condition, disability and death
• A fear of falling may also develop among patients with PD (patients with PD are prone to fall accidents)

• Social anxiety can lead to social isolation
• Which consequently further exacerbates that anxiety
• Isolation and loneliness can lead to feelings of depression, especially in older patients

Treatment

• Treatment for patients with anxiety has a focus on
• Lifestyle modification
• Exercise
• Sleep hygiene
• Nutrition
• Socializing

• Cognitive behavioral therapy (CBT) is also beneficial in the form of mindfulness and meditation

• Pharmacological include:
• Prescription of SSRIs and SNRIs
• Use of benzodiazepines is discouraged due to their adverse side effects

Apathy

Overview and Diagnosis

• Apathy is one of the most frequent symptoms in patients with PD and one of the hardest to treat

• Apathy can be defined as a state of reduced motivation as a result of a reduction in goal-directed behaviour.

• Patients with apathy experience
• Low levels of activity, interests and socialization

• Apathy is sometimes confused as a ‘by-product’ of depression due to overlap in similarities
• Particular thoughts and symptoms that are specific to apathy in the presence and absence of depression that helps differentiate between the two conditions
• Loss of interest and activity in the world
• Lack of concern for others and
• Emotional indifference and reactivity

Etiology

• Apathetic symptoms may precede the worsening of the motor symptoms of PD

• The pathophysiology may be associated with a neuronal disruption in areas of the brain associated with and responsible for goal-directed behavior
• i.e. dopaminergic projections between the frontal cortex and the ventral tegmentum

Treatment

• Engaging in self-care activities (e.g. exercise) will
• Help boost energy levels
• Provide an opportunity for structure and socialization in the patient’s daily routine
• Help with/overcoming apathy symptoms

• Joining a support group for people with PD can also help

• Dopaminergic medications are sometimes effective for apathy
• Dopamine agonist are generally the most effective for apathy among all

• SSRI may also be considered in difficult situations.

Psychosis

Overview and Diagnosis

• About 20 to 40 percent of PD patients experience psychosis during the earlier stages and by the late stages, it may go up to 70 percent

• There is common co-morbidity of cognitive impairment or dementia.

• Positive symptoms of psychosis include:
• Hallucinations
• Illusions
• Delusions

• Hallucinations
• can affect any of the senses
• Visual, auditory, olfactory, tactical, and/or gustatory hallucinations

• By far most common hallucinations are visual (70-90%) with auditory being second most common (up to 10%) and tactile being rare (<1%)

• Delusions
• Beliefs that aren’t grounded in reality
• Not as frequent as hallucinations in PD patients:
• usually 8-10 %
• The most common form is persecutory delusion i.e. the fear that people are out to get you or that your significant other is being unfaithful etc.
• Such beliefs can lead to aggressive behavior where the patient is both a danger to themselves and others
• Delusions are less common than hallucinations, but harder to treat.
• Delusions of grandiosity are unusual for PD.

• Diagnosis of PD Psychosis requires:
• Duration of the psychosis symptoms
• Patients must experience symptoms of hallucinations and delusions for at least a month
• Other preexisting psychiatric conditions
• Not have another condition that could be causing these symptoms (e.g. dementia, delirium, major depression (MDD), or schizophrenia)

Etiology

• The duration and severity of illness, as well as cognitive impairment, make the development of psychosis in PD patients more likely

• Additional risk factors include:
• Depression
• Sleep disorder (insomnia or sleep apnea)
• Visual or hearing problems
• PD medications
• Other medications such as anticholinergic medications.

• There are two possible contributors for developing PD psychosis
• The biochemical changes of neurotransmitters such as serotonin and dopamine
• Imbalance of dopaminergic tone with low serotonergic tone with medications

• Patients with PD have lower than normal levels of dopamine

• Medication to improve mobility increases dopamine levels,

• Psychosis can occur as a side effect of this treatment

Treatment

• Since PD drugs can cause psychosis
• One option will be to reduce the medications if possible
• This is limited by worsening of motor symptoms

• Goals:
• improves movement without causing symptoms of psychosis and
• remove hallucinations and delusions without making the motor symptoms much worse for the patient

• Medications for PD Psychosis:
• pimavanserin (Nuplazid) Only FDA approved options
• Rivastigmine (good benefit on visual hallucination in a large trial)
• Clozapine (highly effective but difficulty to use due to risk of aplastic anemia)
• Seroquel (often use for agitation and insomnia, no benefit on hallucinations based on 7 trials)

Cognitive Impairment and Dementia

Overview and Diagnosis

• Mild cognitive impairment (MCI)
• impairment not enough to affect daily activities.

• Parkinson Disease Dementia (PDD)
• impaired daily activities

• Concomitant Alzheimer's Dementia and other impairment can also occur in PD and should be considered.

• Within the first 3 to 5 years, about 20% and 57% of patients are affected by MCI

• Occurs on a continuum of severity:
• the prevalence increasing with the duration of the disease

• Common pattern of cognitive deficits in PD is considered sub-cortical dysfunction and includes:
• Executive dysfunction
• Poor Attention
• Reduced processing speed
• Impaired Verbal Fluency

Etiology

• Dementia in PD patients was estimated to account for 3.6 of cases of dementia in general

• Incidence rates of over 80% have been found in patients monitored for more than 20 years following the onset of PD

• Patients who have been newly diagnosed with PD are two times more likely to develop MCI as compared to healthy elderly patients

Treatment

• The only medication that has been FDA approved for PDD:
• Rivastigmine, an acetylcholinesterase inhibitor,

• As for MCI:
• there is currently no successful pharmacological treatment.

• important to consider non-biomedical approaches
• exercise and programs that promote cognitive training and simulation

Further Reading

1. Dujardin, K., & Sgambato, V. (2020). Neuropsychiatric Disorders in Parkinson’s Disease: What
Do We Know About the Role of Dopaminergic and Non-dopaminergic Systems?. Frontiers In Neuroscience, 14. doi: 10.3389/fnins.2020.00025

2. Molina Ruiz, R., Evans, A., Velakoulis, D., & Looi, J. (2016). Neuropsychiatric manifestations
of Parkinson’s disease. Australasian Psychiatry, 24(6), 529-533. doi: 10.1177/1039856216654393

Bibliography

1. Apathy. (2021). Retrieved 5 November 2021, from https://www.parkinson.org/Understanding-Parkinsons/Symptoms/Non-Movement-Symptoms-Apathy

2. Jones, S., Torsney, K., Scourfield, L., Berryman, K., & Henderson, E. (2020). Neuropsychiatric symptoms in Parkinson's disease: Aetiology, diagnosis and treatment. BJPsych Advances
26(6), 333-342. doi:10.1192/bja.2019.79

3. Kehagia, A., Barker, R., & Robbins, T. (2010). Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease. The Lancet Neurology, 9(12), 1200-1213. doi: 10.1016/s1474-4422(10)70212-x

4. Parkinson's and mental health. Parkinson's UK. (n.d.). Retrieved November 3, 2021, from https://www.parkinsons.org.uk/information-and-support/parkinsons-and-mental-health.

5. Parkinson's Psychosis: Understanding Symptoms and Treatment. (2021). Retrieved 5 November 2021, from https://www.healthline.com/health/parkinsons/parkinsons-psychosis#hallucinations