It’s estimated that 10 to 47% of adults with a prognosis of schizophrenia additionally expertise ADHD signs (Arican et al., 2018), and kids with ADHD have an elevated danger of creating schizophrenia later in life (Dalsgaard et al., 2020). Folks with a twin prognosis of schizophrenia spectrum dysfunction (SSD) and ADHD usually tend to have difficulties in training and at work (Levy et al., 2015) and expertise extra extreme signs, poorer cognitive operate and elevated social difficulties. Regardless of this, there’s a lack of analysis on the expertise of people with SSD who even have ADHD signs.
ADHD and schizophrenia can have overlapping signs corresponding to difficulties with consideration, planning, studying and restlessness or impulsive behaviour. This will make it tougher for clinicians to obviously distinguish the 2 situations and make correct diagnoses. Misdiagnosis between ADHD and schizophrenia spectrum problems (SSD) and under-diagnosis of the twin situations is a major concern.
Whereas ADHD drugs corresponding to psychostimulants are related to decreased mortality (Vasiliadis et al., 2024), the image is much less clear for folks with SSD and ADHD. Many clinicians are cautious about prescribing psychostimulants due to considerations they may worsen psychotic signs in some folks.
To handle this concern, Luykx et al. (2025) used knowledge from a number of Swedish well being and inhabitants registers to check whether or not ADHD remedy use in people with schizophrenia improved or worsened their well being outcomes over 9 years.
Clinicians are cautious in prescribing ADHD remedy in folks with psychotic problems, however is that backed up by proof of danger?
Strategies
Analysis design
The authors analysed knowledge of 9,416 folks with SSD who used ADHD remedy. SSD included diagnoses of schizophrenia, schizotypal dysfunction, delusional problems, transient psychotic dysfunction, shared psychotic dysfunction, schizoaffective dysfunction and unspecified psychosis based on ICD-10. ADHD drugs studied included methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, atomoxetine and modafinil.
They examined whether or not people who used ADHD remedy had decreased hospitalisation or mortality charges and appeared in additional element at particular hospitalisations corresponding to for psychosis, somatic situations (e.g. pneumonia or epilepsy) or cardiovascular sickness.
Statistical strategies
Analyses had been carried out utilizing a within-individual design with Cox regression fashions evaluating intervals of ADHD remedy use versus non-use throughout the identical particular person for all outcomes. Analyses had been adjusted for time since cohort entry, temporal order of ADHD drugs, and concomitant use of psychotropic medication (antipsychotics, antidepressants, benzodiazepines, temper stabilisers, medication for addictive problems).
In addition they used between-individual Cox fashions evaluating folks utilizing ADHD remedy to these not utilizing remedy, adjusted for age, intercourse, incapacity pension, variety of earlier hospitalisations for psychosis, prognosis of ADHD, substance use dysfunction, earlier suicide makes an attempt and former clozapine use.
They in contrast whether or not antipsychotic use throughout ADHD remedy elevated or decreased danger of hospitalisation and in addition studied dosages of the 2 most used ADHD drugs (methylphenidate and lisdexamphetamine) and their results on outcomes.
The research in contrast intervals of ADHD remedy use and non-use inside and between folks with SSD – and assessed dangers of hospitalisation and mortality, after controlling for quite a lot of demographic variables.
Outcomes
All-cause hospitalisation/mortality
Over the 9 years, lisdexamphetamine was related to decreased danger of being admitted to hospital (for any cause) or dying (from any trigger) whereas high-dose methylphenidate was related to a slight elevated danger particularly in these not taking antipsychotics. Reasonable-dose methylphenidate was related to a decreased danger.
Hospitalisation for psychosis and somatic situations
Atomoxetine was related to decreased danger for psychosis-related hospitalisation. Lisdexamphetamine and moderate-dose methylphenidate was related to decreased danger for hospitalisation for psychosis whereas ADHD polytherapy elevated danger of somatic hospitalisation.
Hospitalisation for heart problems
The research discovered no important associations between any ADHD remedy publicity and cardiovascular hospitalisation.
Dosage issues
The general sample urged that, generally, reasonable dosages of lisdexamphetamine and methylphenidate are usually safer to make use of in SSDs. Quite the opposite, very excessive dosages of methylphenidate (over 95mg/day) carried an elevated danger for hospitalisation and mortality, however this was not matched for lisdexamfetamine.
This analysis means that ADHD remedy (particularly lisdexamphetamine (at any dose) and low to medium doses of long-acting methylphenidate) could also be safer for folks with schizophrenia than many individuals assume.
Conclusion
- Lisdexamphetamine constantly confirmed protecting results throughout doses, displaying the strongest proof for long-term security in people with SSDs.
- Atomoxetine additionally confirmed profit.
- Methylphenidate had a U-shaped danger sample:
- Reasonable doses had been helpful
- Very excessive doses (≥95 mg/day) had been related to elevated danger.
- There was no important impact for lots of the ADHD drugs.
The research affords reassuring findings, particularly for lisdexamphetamine in sufferers with SSD, nevertheless it doesn’t affirm long-term security for all ADHD drugs. Solely lisdexamphetamine use was related to a decreased danger of each all-cause hopitalisation/mortality and somatic hopitalisations. Some drugs present potential danger corresponding to high-dose methylphenidate and ADHD remedy polytherapy i.e. taking greater than 1 ADHD remedy.
As there was no important impact for lots of the ADHD drugs, we don’t have sufficient proof to say if the drugs enhance or lower the danger of hospitalisation.
In folks with SSDs taking ADHD remedy – lisdexamfetamine confirmed the most effective security profile – whereas methylphenidate seems to warrant warning at excessive doses.
Strengths and limitations
The research’s long-term follow-up interval and enormous complete pattern measurement are key strengths; nonetheless it’s unclear whether or not the subset pattern sizes for every ADHD remedy are massive sufficient to be a high-powered research, significantly because it analyses retrospective knowledge alone.
The research’s definiton of “SSDs” is expansive, together with a wide range of situations with some psychotic options – nonetheless this could danger obscuring confounding elements on this research which may be explicit to a dysfunction e.g. schizoaffective dysfunction, the place pervasive temper modifications and in addition antidepressant drugs might individually have an effect on hospitalisations and mortality dangers. Additional, the research statistically adjusts for quite a lot of demographic options and in addition different pharmacological interventions corresponding to earlier clozapine use, it doesn’t explicitly analyse the results of such changes being made – these could have unknown confounding modulating results on the suitability or efficacy of ADHD remedy in SSDs, past what may be gleaned from the paper.
One other limitation is the broad categorisation of security outcomes (e.g., “hospitalisation for psychosis”). The research didn’t discover the impact of ADHD remedy on particular SSD-related signs such because the severity of psychotic signs, explicit discrepancies in optimistic/destructive signs, useful impairments, or high quality of life.
The geographical confinement of this research to Swedish well being programs might additional be a limitation to generalisability of outcomes.
Therefore, though the authors report that they discovered no proof of elevated danger of adversarial outcomes for ADHD drugs in people with a situation underneath the schizophrenia spectrum problems (SSDs), particularly when used with antipsychotics; these findings needs to be interpreted as broadly reassuring, slightly than conclusive. Additional research that are prospectively designed and higher powered to evaluate every ADHD remedy individually, can be helpful to kind conclusions on their long-term security.
The outcomes provide pragmatic reassurance – it is a strong proof-of-concept for additional analysis, prospectively evaluating particular person ADHD drugs in folks with particular person SSDs.
Implications for follow
This analysis means that use of the ADHD drugs lisdexamphetamine, and long-acting methylphenidate at low to medium doses, seems safer than beforehand assumed in people with SSDs. Nevertheless, the authors advise warning with methylphenidate: it ought to usually be prevented in sufferers with SSDs who should not utilizing an antipsychotic, and high-dose methylphenidate (≥95 mg every day) needs to be prevented in all sufferers with SSDs.
For the opposite ADHD drugs examined, amphetamine, dexamphetamine, atomoxetine and modafinil, the research gives inadequate proof to attract agency conclusions about long-term security.
Given the shortage of clear danger knowledge for a lot of drugs, the advantages of successfully treating comorbid ADHD should be rigorously weighed in opposition to potential dangers. Therapy selections needs to be made utilizing a personalised, shared decision-making strategy, considering the person’s psychiatric historical past, present drugs, and danger elements, with the goal of bettering restoration and useful outcomes.
There can also be a coverage influence to this paper – as the availability of lisdexamfetamine in different jurisdictions, specifically Anglophone international locations, may be restricted by follow tips that record it as a second-line remedy for ADHD. Offering its comparable security throughout doses, relative to methylphenidate that is commonly prescribed as a ‘first-line’ remedy, knowledge from this research needs to be used to think about whether or not guideline and coverage reform is warranted, not less than in instances the place an individual needing ADHD remedy additionally experiences an SSD.
Rising proof of security of ADHD drugs in SSDs, particularly lisdexamfetamine which is much less favoured in some international locations – ought to inform not solely particular person medical follow but in addition reform in prescribing tips and coverage.
Assertion of pursuits
None to declare.
References
Major paper
Luykx, J.J., Corbeil, O., Kärkkäinen, O. et al. Long run security of ADHD remedy in sufferers with schizophrenia spectrum problems. Mol Psychiatry 30, 4859–4867 (2025). https://doi.org/10.1038/s41380-025-03080-3
Different references
Arican, I., Bass, N., Neelam, Okay., Wolfe, Okay., McQuillin, A., Giaroli, G., & others. (2019).
Prevalence of consideration deficit hyperactivity dysfunction signs in sufferers with schizophrenia. Acta Psychiatrica Scandinavica, 139(1), 89–96. https://doi.org/10.1111/acps.12948
Dalsgaard, S., Mortensen, P. B., Frydenberg, M., Maibing, C. M., Nordentoft, M., & Thomsen, P. H. (2020). Affiliation between attention-deficit hyperactivity dysfunction in childhood and schizophrenia later in maturity. European Psychiatry, 29(4), 259–263. https://doi.org/10.1016/j.eurpsy.2013.06.004
Gough, A., & Morrison, J. (2016). Managing the comorbidity of schizophrenia and ADHD. Journal of Psychiatry & Neuroscience, 41(5), E79–E80. https://doi.org/10.1503/jpn.150251
Levy E, Traicu A, Iyer S, Malla A, Joober R. Psychotic problems comorbid with attention-deficit hyperactivity dysfunction: an vital information hole. Can J Psychiatry. 2015 Mar;60(3 Suppl 2):S48-52. PMID: 25886680; PMCID: PMC4418622.
Vasiliadis HM, Lunghi C, Rahme E, Rochette L, Gignac M, Massamba V, Diallo FB, Fansi A, Cortese S, Lesage A. ADHD drugs use and danger of mortality and unintentional accidents: a population-based cohort research. Transl Psychiatry. 2024 Feb 28;14(1):128. doi: 10.1038/s41398-024-02825-y. PMID: 38418443; PMCID: PMC10901868.
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