Below is a list of medicines that doctors may sometimes prescribe to treat specific symptoms of PWS (available in NZ as stated, June 2019). This is not a comprehensive list as there may be preferred alternatives or other medicines available. It also does not include treatments for diabetes. Please note the following warnings:
• Some classes of medication (SSRI’s and anti-psychotics/neuroleptics) are more likely to have side effects at standard doses, possibly due to individual drug metabolism differences in PWS.
• The increased risk for disrupted temperature regulation or hyperglycaemia /diabetes mellitus in PWS should be considered with some medications. If a keto diet is followed, the effects of this should also be considered with some medications.
• From PWSA USA Medical Coordinator: Medication Combinations May Fatally Impair Breathing in PWS
“We know that people with PWS often absorb and keep medications in their system longer than the average person. The medications of greatest concern include prescription pain medications, anaesthetics, and psychotropic medications, all of which have the potential to depress breathing in any person. Combinations of several new medications create the most worrisome situation and is most likely to occur after surgery.”
Anxiety / antidepressant medications
Stimulant medications for daytime sleepiness or ADHD (attention, impulsivity)
Anti-psychotic medications for behaviour or psychiatric disorders
Mood stabilising medications
Anti-convulsant / anti-epileptic medications for mood stabilising or behaviour
Benzodiazepines – fast acting anxiety reducing sedatives
Fluoxetine hydrochloride (Arrow-Fluoxetine / PROZAC®)
Fluoxetine belongs to a group of medicines called selective serotonin re-uptake inhibitors (SSRIs) which are used in the general population to treat depression, anxiety and OCD. They are mainly prescribed to adults but may be used for children. In PWS, fluoxetine is often prescribed for reducing anxiety, stabilising behaviour or for depression. Reportedly, SSRIs usually seem to work well for anxiety in PWS and they can be very effective in low doses, but they do not work for everyone and there may be unwanted side effects or a worsening of specific symptoms. Some people with PWS are prone to mood activation with SSRIs. Sometimes initial response may be good but negative effects can be experienced with dose changes. It has also been reported that SSRIs have not been helpful for skin-picking and food preoccupation in PWS. They are also rated as only somewhat effective for temper outbursts. Some other SSRIs used in PWS and available in NZ are Sertraline (brand name Zoloft may be used overseas) and Citalopram (brand name Celexa may be used overseas.)
Amitriptyline belongs to a different anti-depressant medicine group to SSRIs and is classified as a tricyclic antidepressant (TCA). In the general population it is thought to be a very effective antidepressant, but because of it’s higher toxicity, it is usually only used when SSRIs are ineffective. Amitriptyline is not commonly prescribed in PWS, but is sometimes used as an off-label treatment for sleep problems when taken in the evening.
Clonidine hydrochloride (Catapres)
Clonidine is another medicine sometimes used in PWS for its off-label benefits. Clonidine is a centrally acting agent which is indicated by Medsafe for hypertension (high blood pressure), migraines/headaches and vasomotor conditions. However, it is occasionally used for anxiety or sleep problems in PWS. It is also sometimes used as a non-stimulant ADHD treatment and for reducing impulsive aggression. It should be used with caution with other medications.
Melatonin modified-release (CIRCADIN®)
Melatonin may be prescribed to children under 18 years by Special Authority for insomnia secondary to a neurodevelopmental disorder (including, but not limited to, autism spectrum disorder or attention deficit hyperactivity disorder) when behavioural and environmental approaches have been unsuccessfully tried. For some children with PWS, Melatonin may improve sleep quality and help with early waking.
Methylphenidate hydrochloride (RITALIN® / Rubifen / and SR sustained-release)
Methylphenidate is a stimulant medication that may be prescribed by Special Authority to children and adults for narcolepsy (sleep disorder) or ADHD in immediate release or sustained release form. In PWS stimulants can improve impulsivity, daytime sleepiness, focus and attention, but the effects differ for individuals and are dose dependent. Stimulants may also negatively affect perseveration, OCD, anxiety and tics. Additional medications may be needed to find balance. Stimulants are not recommended if patients have pre-existing or are at high risk of developing psychosis, suicidal tendencies or bipolar disorder.
Methylphenidate hydrochloride extended-release (CONCERTA® / RITALIN® LA)
Methylphenidate extended-release is a stimulant medication that may be prescribed by Special Authority for ADHD only, but one of the above formulations need to have been tried first and found to be ineffective. Extended-release formulations are often preferred for easier administration. Anecdotally, some families report good success with Concerta for improving focus and attention. As with all stimulants, effects differ, they are dose dependent, other medications may be needed to find balance and they are not recommended for some patients.
Dexamfetamine is a stimulant medication that may be prescribed by Special Authority to children and adults for narcolepsy or ADHD. (Note: Adderall is a similar brand available overseas.) See the information above regarding stimulants.
Modafinil acts on the central nervous system to promote wakefulness. It may be prescribed by Special Authority for EDS (excessive daytime sleepiness) and narcolepsy, but Methylphenidate or Dexamphetamine needs to have been trialled first. Anecdotally, Modafinil has been very successful for some patients with PWS, but if the dose is too high, anxiety, perseveration or tics may increase and PWS patients may also be prone to negative effects on mood. (Note: brand name Provigil may be used overseas.)
Risperidone (Actavis / RISPERDAL®)
Risperidone belongs to a group of medicines called second generation anti-psychotics (SGAs). All anti-psychotics should be used with caution in PWS, particularly for sedative effect and negative drug interactions, i.e. with pain medications. Risperidone is different to other anti-psychotics because in addition to being used to treat schizophrenia, other psychotic disorders and bipolar disorder, risperidone is also indicated for conduct and disruptive behaviour disorders in children, and for adults with intellectual disability for whom destructive behaviour is prominent. It also has less sedative effect than some SGAs and is less likely to cause heart problems. Therefore, risperidone is often successful in treating severe problem behaviours in PWS, but it does not work for everyone. An unfortunate side effect of SGAs is rapid weight gain and causing metabolic, neurological and hormonal changes. Risperidone has a medium risk for weight gain, diabetes and heart disease, mild to moderate risk for developing permanent tardive dyskinesia (repetitive, involuntary movements) with prolonged or high dose treatment, and the highest SGA risk for elevated prolactin hormone levels causing breast enlargement. If negative side effects are experienced, Aripiprazole (ABILIFY™) has a lower likelihood to cause weight gain, metabolic changes and hormonal changes. It carries a similar risk for tardive dyskinesia. Ziprasidone has a lower risk for weight gain and metabolic changes, plus the lowest risk for tardive dyskinesia. There is limited research on the use of psychiatric medications in PWS but it has been suggested in the past that antidepressants and antipsychotic medication may be more effective than mood-stabilizing medication, however, more recent reports warn that anti-psychotics (and SSRIs) can cause mood activation in PWS. A small case study noted that risperidone had promising treatment effects for psychotic symptoms, mainly associated with uniparental disomy (UPD).
Aripiprazole (Aripiprazole Sandoz)
Aripiprazole (ABILIFY™ overseas brand name) is an SGA for the treatment of schizophrenia and manic or mixed episodes associated with bipolar disorder, with or without psychotic features. It is often used as an alternative to Risperidone or if negative side effects are experienced with Risperidone. Compared to other SGAs, it is more energising as opposed to sedative effect. It also has a lower likelihood to cause weight gain and metabolic changes and has the lowest risk for prolactin hormonal changes. It carries a similar risk to Risperidone for tardive dyskinesia. Abilify was previously available by Special Authority to patients with a diagnosis of ASD or schizophrenia or related psychoses, but since June 2018, Aripiprazole Sandoz has sole supply status and may be prescribed without restriction. Like all anti-psychotic medications, it should be used with particular caution in PWS (see above.)
Ziprasidone is an SGA for the treatment of schizophrenia and manic or mixed episodes associated with bipolar disorder. Like all anti-psychotics, it should be used with particular caution in PWS (see above.) Compared to other SGAs, Ziprasidone has the lowest risk for metabolic side effects and weight gain. It also has a lower risk for tardive dyskinesia compared to risperidone, aripiprazole and olanzapine, and a low risk for increased prolactin levels. However, although this medication does have fewer side effects than similar medications, it does have a risk for causing abnormal heart rhythm so heart problem history and patient health are considered before starting treatment. Long term use could also increase osteoporosis risk.
Olanzapine is an SGA for adults which is prescribed for the treatment of schizophrenia and related psychoses, and for the treatment of manic or depressive episodes associated with bipolar disorder. It is thought that Olanzapine may be effective for PWS patients and is good for treating agitation, but like all anti-psychotics, it should be used with particular caution in PWS (see above.) There have been reported cases of prolonged hypothermia associated with this medication and PWS. Compared to other SGAs, Olanzapine is less likely to cause heart problems, but it has the highest risk for metabolic side effects and weight gain. It may also have more sedative effect than some SGAs. The risk for tardive dyskinesia is similar to risperidone and aripiprazole, but it has a low risk for raising prolactin levels, alongside Quetiapine.
Quetiapine is an SGA indicated for adults only for relieving psychotic symptoms, including schizophrenia, and for manic or depressive episodes associated with bipolar disorder. It has been known to be used in individuals with PWS as a short term treatment for temper outbursts due to its sedative calming qualities. Like all anti-psychotics, it should be used with particular caution in PWS (see above.) Compared to other SGAs, Quetiapine is less likely to cause heart problems, is the least likely to cause tardive dyskinesia and has a low risk for causing hormonal changes, but it has a moderate to high risk for metabolic side effects and weight gain. Overall this medication has fewer side effects, but specific risk factors to consider for PWS are sleep apnoea, aspiration pneumonia, constipation and intestinal obstruction.
Haloperidol is a ‘first generation’ anti-psychotic medication which can be prescribed from 12 years for manic depressive illness and the management of symptoms of psychotic disorders such as schizophrenia or psychosis. It is thought to be sometimes effective for PWS patients, but anti-psychotics should be used with particular caution in PWS patients (see above.) First generation or typical antipsychotics are infrequently used today due to this group having more side effects, particularly affecting motor function, although weight gain risk is low. Haloperidol has the highest risk for elevating prolactin levels. ‘Second generation’ antipsychotics such as risperidone are more or less exclusively used in PWS and are referred to as atypical.
Lithium Carbonate (Lithicarb FC, Priadel, Douglas)
Lithium is classed as an anti-psychotic medication, but is different to those above and is known as a mood stabilising medication. It is an effective mood stabiliser for recurrent mood disorders, for mania, depression or bipolar depression when other anti-depressants have been unsuccessful. It is also known to lower aggression and impulsivity. As with all antipsychotics, it should be used with particular caution in PWS (see above) and interactions with other medications, such as NSAIDS anti-inflammatory pain medications, should be avoided. It is also important that adequate hydration is maintained whilst taking this medication and regular blood tests are recommended to monitor levels for toxicity and check the effects of lithium on the body. Mood stabilising medications are not commonly used in PWS, so there is little data about their effectiveness, but it has been noted that Lithium and Valproate are well tolerated. It has been suggested that Lithium might be one of the most effective long term treatments for mood stabilising in terms of patients being less likely to have a recurrence.
Valproic Acid / Sodium Valproate (Epilim)
Valproic acid is a fatty acid derivative and anti-convulsant primarily used to treat epilepsy and bipolar disorder. It restores the balance of certain natural substances (neurotransmitters) in the brain; GABA levels are increased, a chemical that calms nerve cells. Valproic acid is sometimes used for treating manic episodes and mood stabilisation in PWS when other treatments have been unsuccessful and is reportedly well tolerated. Regular blood tests are recommended to check its effect on the body and liver.
Lamotrigine (Lamictal, Logem)
Lamotrigine is an anti-convulsant medicine used to treat epilepsy and bipolar disorder. It works by blocking certain kinds of nerve activity which reduces seizures and helps with mood disorders. It predominantly prevents mood episodes by preventing depressive episodes, whereas lithium (above) may be better at treating mania. Like lithium, it’s a first-line treatment for bipolar disorder, but its effectiveness in PWS is unknown.
Topirimate is indicated by Medsafe NZ for the control of epilepsy in adults and children. It works by increasing the effect of GABA, a chemical that calms nerve cells in the brain. However, low dose Topirimate has been successful in treating self injury (skin picking) and impulsive/aggressive behaviours in PWS. There are even case study reports of Topiramate reducing food seeking behaviours in some patients. However, Topirimate and some anti-psychotic medications are known to exacerbate osteoporosis (associated with PWS.) In recent years N-acetyl cysteine has become a widely used and mostly successful alternative natural treatment for skin picking, particularly in the form of the supplement ‘PharmaNAC’. (Read more on our supplements page.)
NOTE: All anti-epileptic drugs above can increase risk for hyponatremia in PWS, but Carbamazepine (Tegretol), another anti-convulsant medication also indicated for mood stabilisation (acute mania and bipolar disorders), should be used with additional care due to a higher risk for inducing hyponatremia.
Lorazepam is an anxiolytic or benzodiazepine medication indicated for short term episodes of moderate to severe anxiety. It can also be used for insomnia associated with anxiety. It has a fast acting effect and is therefore sometimes used in PWS for managing a behavioural episode. Negative side effects are drowsiness, memory problems and confusion, and this sedative effect means that it should be used with extra care in PWS. Lorazepam can also be habit forming with withdrawal symptoms experienced if it is taken for a long time and then stopped. Compared to the similar medications of diazepam (Valium) and clonazepam, it is thought that lorazepam could be more effective for PWS because of its shorter acting sedative effect and because it is less likely to interact with other medications. However, lorazepam should not be used if other CNS depressants are taken, i.e. other benzodiazepines, sedatives or sleep medications, due to a higher risk for respiratory depression in PWS.
A new type of service has become available overseas using pharmacogenomics to find an appropriate individual treatment without the need to trial lots of medications first. This type of genetic testing to tailor medication and dosage to the individual is not yet available in New Zealand, but we hope it will be in the future! Check out www.genomind.com, www.genesight.com, www.genelex.com and www.pathway.com