What are the key considerations for prescribing antidepressants in patients with comorbid physical health conditions?

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Posted: 22 August 2025Updated: 22 August 2025 Guideline-Aligned (High Confidence) Clinically Reviewed
Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

When prescribing antidepressants in patients with comorbid physical health conditions, key considerations include:

  • Assess the presence of additional physical health disorders to understand how these may interact with antidepressant treatment and influence side effects.
  • Consider the side effects of antidepressants, particularly that SSRIs may cause or worsen hyponatraemia, especially in older adults.
  • Be aware of drug interactions between antidepressants and medications used for physical health problems; for example, avoid fluvoxamine with theophylline, clozapine, methadone, or tizanidine, and prefer sertraline or citalopram due to fewer interactions.
  • Choose antidepressants carefully, generally starting with an SSRI in generic form unless contraindicated by interactions, with citalopram or sertraline preferred for their lower interaction risk.
  • Avoid certain antidepressants in primary care such as dosulepin, non-reversible MAOIs, combined antidepressants, and lithium augmentation unless prescribed by specialists.
  • Consider toxicity in overdose when selecting an antidepressant, especially in patients at risk of suicide; venlafaxine and tricyclic antidepressants (except lofepramine) have higher overdose risks.
  • Manage interactions with common medications: SSRIs are generally avoided with NSAIDs, warfarin, heparin, aspirin, triptans, and MAO-B inhibitors due to bleeding risk or other adverse effects; alternatives like mirtazapine, mianserin, moclobemide, reboxetine, or trazodone may be safer.
  • Provide thorough patient information about the gradual onset of antidepressant effects, importance of adherence, potential side effects, drug interactions, and discontinuation symptoms, reassuring that addiction does not occur.
  • Prescribe therapeutic doses and avoid subtherapeutic dosing in patients with chronic physical health problems.
  • Monitor patients regularly after starting antidepressants, with earlier and more frequent follow-up for those at increased suicide risk or younger than 30 years.
  • Collaborate closely with physical health services and seek specialist advice if uncertain about drug interactions or complex cases.

These considerations aim to optimise depression treatment while minimising risks related to comorbid physical illnesses and polypharmacy.

References:

Educational content only. Always verify information and use clinical judgement.