Neuropsychiatric symptoms in Parkinson's Disease

Behavioural Neurology
Movement Disorder
Ready to Publish
Ready to Publish
Publish on
Nov 21, 2021
Project Lead
2nd Author
Parkinson's Disease
Ramsha Tariq MBBS, Danish Bhatti MD


  • 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


  • 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


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)


  • 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


  • 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


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


  • 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 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


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


  • 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


  • 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.


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)


  • 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


  • 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


  • 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


  • 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
    1. Do We Know About the Role of Dopaminergic and Non-dopaminergic Systems?. Frontiers In Neuroscience, 14. doi: 10.3389/fnins.2020.00025
  1. Molina Ruiz, R., Evans, A., Velakoulis, D., & Looi, J. (2016). Neuropsychiatric manifestations
    1. of Parkinson’s disease. Australasian Psychiatry, 24(6), 529-533. doi: 10.1177/1039856216654393


  1. Apathy. (2021). Retrieved 5 November 2021, from
  1. Jones, S., Torsney, K., Scourfield, L., Berryman, K., & Henderson, E. (2020). Neuropsychiatric symptoms in Parkinson's disease: Aetiology, diagnosis and treatment. BJPsych Advances
    1. 26(6), 333-342. doi:10.1192/bja.2019.79
  1. 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
  1. Parkinson's and mental health. Parkinson's UK. (n.d.). Retrieved November 3, 2021, from
  1. Parkinson's Psychosis: Understanding Symptoms and Treatment. (2021). Retrieved 5 November 2021, from
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