Background: Current diagnostic systems of mental disorders are criticized for their poor validity and reliability, owing to the within disorder heterogeneity and between disorder homogeneity. The issue is important if treatments for mental disorders are to be tailored to individual needs. There is little information in this area on perinatal depression (PND), a highly prevalent condition globally.Aims: i) Quantify heterogeneity attributable to the polythetic diagnostic framework for PND and, ii) present evidence for the effectiveness of a multicomponent and low-intensity cognitive behavioral Thinking Healthy Programme (THP) across the heterogeneous presentations of PND.Methods: This investigation presents secondary analyses of a cluster randomized controlled trial, conducted in Kallar Syedan, Pakistan. A total of 903 pregnant women were randomized to an intervention group receiving the THP intervention or control group receiving enhanced usual care. Principal component analyses and clustering algorithm were utilized to identify heterogenous subtypes of PND. Linear mixed effects models were used to assess effectiveness of the intervention across the identified subtypes of PND.Results: Four different clusters of PND were identified: mixed anxiety-depression, somatic depression, mild depression, and atypical depression. All clinical phenotypes responded well to the THP intervention. Compared to their counterparts in the control group, mothers with mild depression in the treatment group yielded lowest risk ratios 0.24 (95% CI: 0.15 to 0.37), followed by mothers with anxiety-depression 0.50 (95% CI: 0.37 to 0.68), atypical depression 0.51 (95% CI: 0.27 to 0.99) and somatic depression 0.59 (95% CI: 0.42 to 0.83).Conclusion: The Thinking Healthy Programme was found to be effective in reducing severity of depressive symptoms and disability across the four subtypes of PND.