Dopamine dysregulation syndrome

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Dopamine dysregulation syndrome
Two-dimensional skeletal formula of the dopamine molecule. Dopamine receptor agonists mediate the development of DDS.

Dopamine dysregulation syndrome (DDS) is a dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time. It typically occurs in people with Parkinson's disease (PD) who have taken dopamine agonist medications for an extended period of time. It is characterized by problems such as addiction to medication, gambling, or sexual behavior.[1]

Signs and symptoms

Punding, a possible symptom of DDS, is the repetition of complex motor behaviors such as collecting or arranging objects.
A slot machine, commonly used for gambling.

The most common symptom is craving for dopaminergic medication. However other behavioral symptoms can appear independently of craving or co-occur with it.[2] Craving is an intense impulse of the subject to obtain medication even in the absence of symptoms that indicate its intake.[2] To fulfill this need the person will self-administer extra doses. When self-administration is not possible, aggressive outbursts or the use of strategies such as symptom simulation or bribery to access additional medication can also appear.[2]

compulsive shopping, eating disorders and hypersexuality.[2] Behavioral disturbances, most commonly aggressive tendencies, are the norm. Psychosis is also common.[2]

Causes

Parkinson's disease is a common

L-Dopa) or dopamine agonists (such as pramipexole or ropinirole) to patients. Dopamine replacement therapy is well known to improve motor symptoms but its effects in cognitive and behavioral symptoms are more complex.[3] Dopamine has been related to the normal learning of stimuli with behavioral and motivational significance, attention, and most importantly the reward system.[4] In accordance with the role of dopamine in reward processing, addictive drugs stimulate dopamine release.[4] Although the exact mechanism has yet to be elucidated, the role of dopamine in the reward system and addiction has been proposed as the origin of DDS.[4] Models of addiction have been used to explain how dopamine replacement therapy produces DDS.[2] One of these models of addiction proposes that over the usage course of a drug there is a habituation to the rewarding effects that it produces at the initial stages. This habituation is thought to be dopamine mediated. With long-term administration of L-dopa the reward system gets used to it and needs higher quantities. As the user increases drug intake there is a loss of dopaminergic receptors in the striatum which acts in addition to an impairment in goal-direction mental functions to produce an enhancement of sensitization to dopamine therapy. The behavioral and mood symptoms of the syndrome are produced by the dopamine overdose.[4]

Diagnosis

Diagnosis of the syndrome is clinical since there are no laboratory tests to confirm it. For diagnosis a person with documented responsiveness to medication has to increase medication intake beyond dosage needed to relieve their parkinsonian symptoms in a pathological addiction-like pattern. A current mood disorder (depression, anxiety, hypomanic state or euphoria), behavioral disorder (excessive gambling, shopping or sexual tendency, aggression, or social isolation) or an altered perception about the effect of medication also have to be present.[5] A questionnaire on the typical symptoms of DDS has also been developed and can help in the diagnosis process.[6]

Prevention

The main prevention measure proposed is the prescription of the lowest possible dose of dopamine replacement therapy to individuals at risk.[4] The minimization of the use of dopamine agonists, and of short duration formulations of L-Dopa can also decrease risk of the syndrome.[4]

Management

First choice management measure consists in the enforcement of a dopaminergic drug dosage reduction. If this decrease is maintained, dysregulation syndrome features soon decrease.[4] Cessation of dopamine agonists therapy may also be of use.[7] Some behavioral characteristics may respond to psychotherapy; and social support is important to control risk factors. In some cases antipsychotic drugs may also be of use in the presence of psychosis, aggression, gambling or hypersexuality.[4]

Based upon five case reports,

valproic acid may have efficacy in controlling the symptoms of levodopa-induced DDS that arise from the use of levodopa for the treatment of Parkinson's disease.[10][11][12]

Epidemiology

DDS is not common among PD patients. Prevalence may be around 4%.

affective disorder.[2]

History

PD was first formally described in 1817;[13] however, L-dopa did not enter clinical practice until almost 1970.[14][15] In these initial works there were already reports of neuropsychiatric complications.[15] During the following decades cases featuring DDS symptoms in relation to dopamine therapy such as hypersexuality, gambling or punding, appeared.[16][17][18] DDS was first described as a syndrome in the year 2000.[19] Three years later the first review articles on the syndrome were written, showing an increasing awareness of the DDS importance.[1][4][2] Diagnostic criteria were proposed in 2005.[5]

Notes

  1. ^
    PMID 17988927
    .
  2. ^
    S2CID 13529178
    .
  3. S2CID 329869
    .
  4. ^
    S2CID 24639862
    .
  5. ^
    S2CID 43149358
    .
  6. S2CID 30088273
    .
  7. S2CID 29101333
    .
  8. S2CID 21544457
    .
  9. PMID 25093777
    .
  10. PMID 25114917
    .
  11. PMID 24288035
    .
  12. PMID 24313567
    .
  13. PMID 11983801
    .
  14. PMID 5637779
    .
  15. ^
    PMID 5820999
    .
  16. S2CID 7648968
    .
  17. S2CID 1107353
    .
  18. S2CID 35486805
    .
  19. PMID 10727476
    .
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