Patients are being harmed because we are not talking about the adverse effects of mental health medicines.

Medicines prescribed for mental health can have disturbing adverse effects.

Sexual dysfunction can be a by-product and in turn adversely affect relationships. Weight gain can lead to non-adherence with prescribed medicines. Other detrimental physical ramifications from medicines to treat mental health conditions including schizophrenia, depression, bipolar disease and withdrawals from them can lead to dry mouth and thirst, tiredness, mood swings – even suicidal ideation.

Issues with medicine safety including the lack of recognition of such adverse effects of medicines prescribed for mental health conditions, a lack of understanding of the impairment that can result from these adverse effects on daily life are the subject of a new report commissioned by PSA.

The Medicine Safety: mental health care report¹ launched this month also found people with mental health conditions were the subject of frequent changes in therapy. There was also little information on how to use medicines safely for these conditions and a failure to document past therapeutic failures and outcomes in many cases. Antidepressants and antipsychotics were also implicated in overdose deaths.¹

A set-and-forget mentality for medicines prescribed for mental health conditions was found by the University of South Australia researchers, with little review for eventual tapering off or stepping up to a new dosage for more therapeutic effect. Patients may be locked into taking these medicines for long periods, which can significantly impede their quality of life.

Tellingly, the report found: ‘The [adverse] effects of most concern to health professionals are not necessarily those that concern the people taking medicines to treat mental health concerns, and the converse is also true.’

Master Mental Health First Aid (MHFA) Instructor and University of Sydney (USyd) Associate Professor Claire O’Reilly FPS says that with increased diagnoses comes heightened mental health medicine use year on year in Australia.

‘We’re getting better at treating mental illnesses,’ she says. ‘More people might be seeking help so medicines are prescribed.’

The report also found that one in two Australians will experience a mental health condition in their lifetime, says its lead author Dr Anna Kemp-Casey, a Research Fellow at the University of South Australia’s Quality Use of Medicines and Pharmacy Research Centre.

‘It will either be us or someone we love who is affected,’ she says.

Crippling adverse effects

Of crucial concern are the conversations that are not had between healthcare professionals and patients about adverse effects from mental health medicines. 

The researchers found that people attending mental health facilities who were taking antipsychotics reported up to seven adverse effects each – most commonly daytime tiredness, weight gain and thirst.

One in four patients on antidepressants reported ‘very’ or ‘extremely’ bothersome adverse effects.

Of great concern is the statistic found that more than 40% of mental health facilities do not have any medicines handover at discharge.

Mental health-related hospitalisations usually last much longer than average hospital stays. In 2020–21 the national average stay in a public hospital with specialised psychiatric care was about 16 days compared to about 6 days.²

This is where pharmacists can step up. ‘Medicine reconciliations are important when a person has been recently discharged from a mental health facility,’ A/Prof O’Reilly told Australian Pharmacist.

‘Community pharmacists have a really important role to ensure ongoing supply of medicines, ensuring there is no confusion about old medicines and support with adherence. The first few months after discharge from hospital are a critical time. Pharmacists can have ongoing conversations and check-ins to ensure that patients are adjusting back into the community.’

Physical health care and monitoring other illnesses e.g. diabetes once they are discharged, should also take place.

Patients with adverse effects may also be good candidates for MedsChecks in the pharmacy or may need referrals for Home Medicines Reviews, A/Prof O’Reilly says.

‘Every patient visit for a repeat script is an opportunity to ask, “is the medicine working? Are there any adverse effects? Is there anything you want to ask me?”’

‘People talk about relationship breakdowns from sexual dysfunction,’ Dr Kemp-Casey points out. ‘They report this in surveys but are often too embarrassed to discuss it with prescribers. Women won’t mention sexual dysfunction to clinicians, unless they are asked directly,’ she stresses.

‘So this is important for addressing adverse effects [that] people find difficult to vocalise.’

A/Prof O’Reilly points to someone diagnosed with schizophrenia in their early 20s who starts on an antipsychotic and who might put on 10–20 kilograms in weight in the first 3–6 months.

As medicine experts, pharmacists can point to medicines less likely to cause particular adverse effects at a population level. This is an important role for GP pharmacists at the point of prescribing, or during monitoring after therapy initiation.

Therapeutic Guidelines are a good place to access good comparative information on mental health medicines,’ notes A/Prof O’Reilly. Pharmacists can have a conversation about the adverse effects patients are experiencing and can offer to contact the prescriber to discuss concerns.

Dr Kemp-Casey suggests it is helpful for prescribers to know what has or has not worked before and ‘also really helpful’ if people can explain their priorities. For instance, for some people a sedating medicine is much less concerning than sexual dysfunction, or the opposite might be true, she says.

‘For people who have lost substantial amounts of weight due to their mental health concern, a medicine that will lead to weight gain is not necessarily a problem. So it all comes down to the individual and what is tolerable for them.’

Pharmacists also have useful tips to reduce the severity of adverse effects.

‘With antipsychotics, pharmacists might say, “The dry mouth is worse for the first 6 hours. If you take it before you go to bed you might not notice it,”’ she says.

Medicine changes

One particular problem highlighted by the report is the high number of medicine changes for people who are inpatient admissions in psychiatric facilities.¹

Some patients are already on multiple medicines. And the report noted there are no Australian studies on the extent of hospital admissions for mental health concerns due to problems with medicines.¹

Average mental health hospitalisations involve 10 medicine changes, including dosage adjustments, adding new medicines and withdrawing others, according to one Australian study.³

‘Some people had up to 32 medicine changes during their admission,’ PSA’s report stated.

‘Four out of 10 charted medicine changes were not recorded at all in the clinical notes,’ it added, and no reason was recorded for 56% of medicine changes. 

Clinical notes for patients with mental health problems are often not up to date, including the recording of adverse effects, or reasons for changes to medicines.

Tellingly, the report stated that only 4% of clinical notes on medicine changes mentioned adverse effects.¹

Patients may also not receive adequate handover about medicine changes during transitions of care. This highlights the dearth of pharmacists in mental health wards to follow up on missing clinical notes or explain new medicine regimens to patients, says Dr Kemp-Casey.

‘There’s a need to train and embed more pharmacists in these facilities.’

The PSA report suggests pharmacist ‘participation in ward rounds in the mental health setting has been shown to lead to dosage adjustments’ for better results after pharmacist recommendations, as well as medicine initiation and discontinuation.

Pharmacists embedded in community mental health teams could also support the hospital discharge process and facilitate regular medication reviews within the service. 

Community pharmacy relationships with these teams are also important.

Says A/Prof O’Reilly: ‘When case managers liaise with community pharmacies or collect DAAs, the pharmacy may be alerted directly by the hospital on discharge about changes to medicines in that process.’

Difficulty withdrawing

For a single episode of depression, an antidepressant should be used for 6–12 months.⁶

But the discontinuation effects of these medicines make it difficult to stop. ‘Withdrawal effects can mimic the condition patients are using the medicines for,’ says Dr Kemp-Casey.

The severity of withdrawal effects is often down to how medicines are metabolised. ‘There are around 150 different versions of the genes that make a liver enzyme responsible for metabolising antipsychotics and antidepressants,’ she says.⁷

‘Some people can discontinue medicines with no issues, whereas others are intensely sensitive.’ 

Genetic tests should soon allow prescribers and pharmacists to identify the medicines that render patients at higher risk of experiencing adverse and withdrawal effects.⁸

For now, as GP pharmacists’ roles continue to grow, they can help to reduce the impacts, says A/Prof O’Reilly.

‘They can monitor and support slow tapering of doses when patients change or come off antidepressants.’

Pharmacists can also help patients distinguish between a relapse in depression and withdrawal effects (see Box 1). 

‘Asking patients if they’re experiencing physical symptoms such as excessive sweating or brain zaps is often the clue that it’s discontinuation, not a relapse of the underlying condition,’ says Dr Kemp-Casey. 

Preventable hospital admissions

Long-term medicines are the mainstay of treatment for patients with severe and persistent mental illnesses (SPMI) including schizophrenia.

But adverse effects from medicines such as antipsychotics or difficult medicine regimens can lead patients to stop taking them all together.

‘Non-adherence, even for a couple of days, could lead to a relapse in symptoms and admission into hospital,’ says A/Prof O’Reilly. To support adherence, pharmacists need to be positioned wherever medicines are.

‘This begins with inpatient stays in hospital, where pharmacists can address adverse effects while patients are in a supportive environment,’ she says.

The need for expanded pharmacist roles within multidisciplinary mental health clinics was highlighted in a 2023 Australian scoping review of studies on pharmacist interventions in medication adherence in patients with mental health disorders.⁸

James Cook University researchers also called for more training in psychiatric pharmacotherapy so pharmacists can ‘confidently’ improve medicine adherence for mental health patients. ‘Engagement in MDTs (multidisciplinary teams) and integrating pharmacists into mental health clinics showed improvements in medication adherence, and clinical outcomes, including reduced depression severity, reductions in polypharmacy and reduced re-hospitalisations,’ the review found. 

‘Similar outcomes,’ that same review concluded ‘have been demonstrated in an Australian scoping review on clinical pharmacists working in mental health hospital-in-the-home teams, where embedding pharmacists in MDTs improved medication adherence and resolved medication-related problems through four key tasks: clinical pharmacy, mental healthcare, home medicines review and facilitating transitions of care through reconciliation of medications and follow-up.’⁹

As well, PSA’s report found: ‘The best place for delivery of pharmacy services for mental health in primary care may vary, as while some services may be relevant for community pharmacy practice or the home, others might need to occur within the clinic setting. Models of pharmacist services to the homeless populations are being explored as are specialist mental health pharmacist services in general practice.’¹

Pharmacists’ roles in transitions of care are key, including facilitating timely access to medication reviews.

All transitions of care are a risky time for medication misadventure, A/Prof O’Reilly points out, but with mental health hospitalisations generally longer² than other hospital stays and often with multiple medicines prescribed, some people may require more support adjusting back to the community.

‘They may have a dose administration aid from the pharmacy but have leftover tablets from the hospital that causes confusion. Or their medicines may take a while – sometimes 6–8 weeks – to start to take effect,’ she adds.

‘That critical time post-discharge is an important time to review needs, duplications, things that are not working and, importantly, adverse effects.’

University of Sydney pharmacy lecturer and researcher Dr Jack Collins MPS says that when pharmacists have a community mental health centre close by, building a relationship with the team is crucial. 

He works in a pharmacy at Artarmon on Sydney’s North Shore with close ties to a local community mental health team.

‘We pack their DAAs and do a lot of medication management for their clients.’ This includes stocking medicines used by the service’s clients.

‘We always have various strengths of injectable antipsychotics in stock, and we dispense clozapine, so the mental health team knows there’s a close-by pharmacy where they can access these medicines,’ says Dr Collins.

Some clients with SPMI who are supported by the local community mental health centre come into his pharmacy to collect their medicine. ‘We take the time to engage with them; see how they’re going,’ he says. Patients and case managers may sometimes come to the pharmacy for discussions, which can include the routine provision of services such as MedsChecks, flu vaccination, and COVID-19 boosters.

Physical healthcare gaps

People living with SPMI often experience gaps accessing care.

‘They might see a psychiatrist and pick up medicines from a community pharmacy, but they don’t have a GP looking at their physical health,’ says A/Prof O’Reilly.

Adverse effects from medicines and ongoing symptoms of SPMI can prevent individuals taking care of themselves. A recent intervention to improve pharmacy- led support systems was the Bridging the gap between physical and mental illness in community pharmacy (PharMIbridge) randomised controlled trial, held across four Australian regions from September 2019 to December 2021.¹⁰ ‘Intervention pharmacists received training on managing physical health, psychotropic medicine adverse effects, goal planning and motivational interviewing,’ says Dr Collins.

Pharmacists began the intervention with a thorough medicine review and an assessment of unmet health needs.

‘The pharmacist and the consumer,’ he says, ‘then worked together to form goals for the following 6 months, with individualised check-ins at various time points.’ A post-intervention survey revealed participants had an overall better quality of life than those in the comparator group, who received just a MedsCheck.¹¹

PharMIbridge is currently undergoing assessment through the Medical Services Advisory Committee.

Too much prescribing

For mild-to-moderate mental health conditions, including anxiety or depression, medicine isn’t typically recommended as first-line treatment.¹²

‘But data suggest around a third of people taking antidepressants wouldn’t meet the clinical criteria for this treatment,’ says Dr Kemp-Casey.¹³

Psychotherapy is the most effective treatment for these patients. Yet accessing a psychologist can be difficult, particularly in rural and remote areas. Patients still face substantial out-of-pocket costs even with a Mental Health Treatment Plan.

‘If someone presents in distress and it’s an 8-week wait for a psychologist that person can’t afford to see, medication looks like a pretty good option,’ she says.

Polypharmacy in mental health treatment is also an issue. ‘More than one psychotropic medicine is often prescribed for patients,’ says A/Prof O’Reilly. ‘While in some cases that may be appropriate, there’s not many guidelines that suggest its efficacy.’ With early intervention a central focus in mental health management, pharmacist involvement in a number of settings is key when medicines are used as part of that intervention.

‘We often see discrepancies in records between what the GP, community pharmacy or hospital thinks a patient is taking,’ says A/Prof O’Reilly. ‘The medication reconciliation process would improve medicine safety, including identifying overprescribing, out-of-range dosages, polypharmacy or missing therapies.’

For more information, visit Medicine Safety: mental health care at: psa.org.au/advocacy/working-for-our-profession/medicine-safety/mental_health/

Clozapine in the community Sydney-based community pharmacy Nick Logan Pharmacist Advice supplies clozapine to 70 patients with treatment-resistant schizophrenia. Servicing this ‘disproportionately large’ cohort of patients is due to strong ties with the Assertive Outreach team at nearby Royal North Shore Hospital, says owner Nick Logan MPS. Mr Logan describes clozapine as a ‘fabulous drug’ that has low extrapyramidal adverse effects, including less akathisia, tremor and little-to-no dystonia or rigidity.4 But due to potentially fatal complications – including agranulocytosis, neutropenia and myocarditis – the medicine is only indicated for patients who have tried and failed using other antipsychotics to manage their condition.4 After screening for cardiovascular problems, a weekly blood test that monitors white blood cell count and neutrophils is required for the first 18 weeks when clozapine is initiated. Once stabilised, patients join the community clozapine system, with a blood test required every 28 days within 48 hours of medicine supply. Within clozapine monitoring software, there are green, amber and red ranges to inform pharmacists whether it’s safe [from blood test results] to supply. In a ‘perfect world’, patients would always be in the green range. But there are always aberrations. ‘For example, if a patient is in the yellow range, bi-weekly blood tests are required and you can only supply enough clozapine to last the patient until the next test,’ says Mr Logan. Clozapine patients usually drop into the pharmacy around once a week, which they consider a safe space. ‘One patient who has complete meltdowns sometimes freezes in the middle of the shopping village,’ he said. ‘Then she comes into the pharmacy and we offer her a seat and a glass of water, which usually helps her regain control.’ Three of Mr Logan’s clozapine patients managed to drastically improve their quality of life through the patient-pharmacist relationship. ‘They used to chain smoke, drink bourbon and smoke marijuana,’ he said. ‘But by forming relationships with the pharmacists, they had someone to ask about their blood glucose levels or why they were starting an oral hypoglycemic. We also gave them feedback on lifestyle changes and how to reduce their blood pressure.’ The patients have since quit cigarettes and alcohol, regularly go to the gym, and have significantly reduced their comorbidities. ‘It’s extremely satisfying from a pharmacist point of view, because you see those improvements,’ said Mr Logan.

References

1. Pharmaceutical Society of Australia. Medicine Safety: mental health care. 2023. At: psa.org.au/advocacy/working-for-our-profession/medicine-safety/mental_health/
2. Australian Institute of Health and Welfare. Mental health. Admitted patients mental health-related care. 2023. At: aihw.gov.au/mental-health/topic-areas/admitted-patients
3. Peusschers E, Twine J, Wheeler A, et al. Documentation of medication changes in inpatient clinical notes: an audit to support quality improvement. Australas Psychiatry 2015;23(2):142–6.
4. Gerlach J, Lublin H, Peacock L. Extrapyramidal symptoms during long-term treatment with antipsychotics. Neuropsychopharmacology At: www.nature.com/articles/1380439
5. New South Wales Health, South Eastern Local Health District.
   Clozapine:  Guidelines for prescribing, administration and monitoring. 2019. At: www.seslhd.health.nsw.gov.au/sites/default/files/documents/SESLHDPR%20591%20-%20Clozapine%20-%20Guidelines%20for%20Prescribing%2C%20Administration%20and%20Monitoring.pdf
6. Wallis KA, Donald M, Moncrieff J. Antidepressant prescribing in general practice: A call to action. Aust J Gen Pract 2021. At: www1.racgp.org.au/ajgp/2021/december/antidepressant-prescribing-in-general-practice
7. Bertilsson L, Dahl ML, Dalén P, et al. Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol 2002;53(2):111–22.
8. Griffith University. PharMIbridge: Bridging the gap between physical and mental illness in community pharmacy. Griffith University. At: griffith.edu.au/menzies-health-institute-queensland/our-research/pharmibridge
9. Syrnyk M, Glass B. Pharmacist interventions in medication adherence in patients with mental health disorders: a scoping review. Int J Pharm Pract 2023; 31(5):449–58.
10. Griffith University. PharMIbridge: Bridging the gap between physical and mental illness in community pharmacy. Griffith University. At: griffith.edu.au/menzies-health-institute-queensland/our-research/pharmibridge
11. Griffith University. Bridging the gap between physical and mental illness in community pharmacy (PharMIbridge) Project Public Summary. 2023.
12. Karrouri R, Hammani Z, Benjelloun R, et al. Major depressive disorder: Validated treatments and future challenges. World J Clin Cases 2021;9(31):9350–67. At: ncbi.nlm.nih.gov/pmc/articles/PMC8610877/ [2]
13. David V, Fylan B, Bryant E, et al. An analysis of pharmacogenomic-guided pathways and their effect on medication changes and hospital admissions: a systematic review and meta-analysis. Front Genet 2021;12:698148. At: ncbi.nlm.nih.gov/pmc/articles/PMC8362615/