It’s estimated that 10 to 47% of adults with a analysis of schizophrenia additionally expertise ADHD signs (Arican et al., 2018), and youngsters with ADHD have an elevated danger of creating schizophrenia later in life (Dalsgaard et al., 2020). Individuals with a twin analysis of schizophrenia spectrum dysfunction (SSD) and ADHD usually tend to have difficulties in schooling and at work (Levy et al., 2015) and expertise extra extreme signs, poorer cognitive perform 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 may 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 big concern.
Whereas ADHD drugs corresponding to psychostimulants are related to lowered 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 might worsen psychotic signs in some folks.
To handle this concern, Luykx et al. (2025) used information from a number of Swedish well being and inhabitants registers to check whether or not ADHD medicine use in people with schizophrenia improved or worsened their well being outcomes over 9 years.
Clinicians are cautious in prescribing ADHD medicine in folks with psychotic problems, however is that backed up by proof of danger?
Strategies
Analysis design
The authors analysed information of 9,416 folks with SSD who used ADHD medicine. SSD included diagnoses of schizophrenia, schizotypal dysfunction, delusional problems, transient psychotic dysfunction, shared psychotic dysfunction, schizoaffective dysfunction and unspecified psychosis in keeping with ICD-10. ADHD drugs studied included methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, atomoxetine and modafinil.
They examined whether or not people who used ADHD medicine had lowered hospitalisation or mortality charges and regarded in additional element at particular hospitalisations corresponding to for psychosis, somatic situations (e.g. pneumonia or epilepsy) or cardiovascular sickness.
Statistical strategies
Analyses have been performed utilizing a within-individual design with Cox regression fashions evaluating intervals of ADHD medicine use versus non-use inside the similar particular person for all outcomes. Analyses have been adjusted for time since cohort entry, temporal order of ADHD drugs, and concomitant use of psychotropic medicine (antipsychotics, antidepressants, benzodiazepines, temper stabilisers, medicine for addictive problems).
In addition they used between-individual Cox fashions evaluating folks utilizing ADHD medicine to these not utilizing medicine, adjusted for age, intercourse, incapacity pension, variety of earlier hospitalisations for psychosis, analysis of ADHD, substance use dysfunction, earlier suicide makes an attempt and former clozapine use.
They in contrast whether or not antipsychotic use throughout ADHD medicine elevated or decreased danger of hospitalisation and likewise studied dosages of the 2 most used ADHD drugs (methylphenidate and lisdexamphetamine) and their results on outcomes.
The examine in contrast intervals of ADHD medicine use and non-use inside and between folks with SSD – and assessed dangers of hospitalisation and mortality, after controlling for various demographic variables.
Outcomes
All-cause hospitalisation/mortality
Over the 9 years, lisdexamphetamine was related to lowered 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 lowered danger.
Hospitalisation for psychosis and somatic situations
Atomoxetine was related to lowered danger for psychosis-related hospitalisation. Lisdexamphetamine and moderate-dose methylphenidate was related to lowered danger for hospitalisation for psychosis whereas ADHD polytherapy elevated danger of somatic hospitalisation.
Hospitalisation for heart problems
The examine discovered no vital associations between any ADHD medicine publicity and cardiovascular hospitalisation.
Dosage issues
The general sample recommended that, normally, average dosages of lisdexamphetamine and methylphenidate are typically 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 medicine (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 persistently confirmed protecting results throughout doses, exhibiting the strongest proof for long-term security in people with SSDs.
- Atomoxetine additionally confirmed profit.
- Methylphenidate had a U-shaped danger sample:
- Reasonable doses have been useful
- Very excessive doses (≥95 mg/day) have been related to elevated danger.
- There was no vital impact for most of the ADHD drugs.
The examine presents reassuring findings, particularly for lisdexamphetamine in sufferers with SSD, but it surely doesn’t verify long-term security for all ADHD drugs. Solely lisdexamphetamine use was related to a lowered danger of each all-cause hopitalisation/mortality and somatic hopitalisations. Some drugs present potential danger corresponding to high-dose methylphenidate and ADHD medicine polytherapy i.e. taking greater than 1 ADHD medicine.
As there was no vital impact for most of the ADHD drugs, we don’t have sufficient proof to say if the drugs improve or lower the chance of hospitalisation.
In folks with SSDs taking ADHD medicine – lisdexamfetamine confirmed the most effective security profile – whereas methylphenidate seems to warrant warning at excessive doses.
Strengths and limitations
The examine’s long-term follow-up interval and huge complete pattern measurement are key strengths; nonetheless it’s unclear whether or not the subset pattern sizes for every ADHD medicine are giant sufficient to be a high-powered examine, notably because it analyses retrospective information alone.
The examine’s definiton of “SSDs” is expansive, together with a wide range of situations with some psychotic options – nonetheless this could danger obscuring confounding components on this examine that could be explicit to a dysfunction e.g. schizoaffective dysfunction, the place pervasive temper adjustments and likewise antidepressant drugs might individually have an effect on hospitalisations and mortality dangers. Additional, the examine statistically adjusts for various demographic options and likewise different pharmacological interventions corresponding to earlier clozapine use, it doesn’t explicitly analyse the consequences of such changes being made – these might have unknown confounding modulating results on the suitability or efficacy of ADHD medicine 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 examine didn’t discover the impact of ADHD medicine on particular SSD-related signs such because the severity of psychotic signs, explicit discrepancies in optimistic/destructive signs, purposeful impairments, or high quality of life.
The geographical confinement of this examine 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 beneath the schizophrenia spectrum problems (SSDs), particularly when used with antipsychotics; these findings must be interpreted as broadly reassuring, somewhat than conclusive. Additional research that are prospectively designed and higher powered to evaluate every ADHD medicine individually, shall be helpful to type conclusions on their long-term security.
The outcomes supply 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. Nonetheless, the authors advise warning with methylphenidate: it ought to typically be averted in sufferers with SSDs who should not utilizing an antipsychotic, and high-dose methylphenidate (≥95 mg day by day) must be averted in all sufferers with SSDs.
For the opposite ADHD drugs examined, amphetamine, dexamphetamine, atomoxetine and modafinil, the examine offers inadequate proof to attract agency conclusions about long-term security.
Given the dearth of clear danger information for a lot of drugs, the advantages of successfully treating comorbid ADHD must be rigorously weighed in opposition to potential dangers. Remedy selections must be made utilizing a personalised, shared decision-making strategy, making an allowance for the person’s psychiatric historical past, present drugs, and danger components, with the intention of bettering restoration and purposeful outcomes.
There can also be a coverage affect to this paper – as the availability of lisdexamfetamine in different jurisdictions, specifically Anglophone nations, may be restricted by follow tips that record it as a second-line medicine for ADHD. Offering its comparable security throughout doses, relative to methylphenidate that is commonly prescribed as a ‘first-line’ medicine, information from this examine must be used to contemplate whether or not guideline and coverage reform is warranted, no less than in instances the place an individual needing ADHD medicine additionally experiences an SSD.
Rising proof of security of ADHD drugs in SSDs, particularly lisdexamfetamine which is much less favoured in some nations – ought to inform not solely particular person scientific follow but in addition reform in prescribing tips and coverage.
Assertion of pursuits
None to declare.
References
Main paper
Luykx, J.J., Corbeil, O., Kärkkäinen, O. et al. Long run security of ADHD medicine 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, Ok., Wolfe, Ok., 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 necessary 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 examine. Transl Psychiatry. 2024 Feb 28;14(1):128. doi: 10.1038/s41398-024-02825-y. PMID: 38418443; PMCID: PMC10901868.
