Imipramine class tricyclic antidepressants have low ionization efficiencies that make them difficult to detect by using secondary ion mass spectrometry. Ultraviolet picosecond laser desorption postionization (ps-LDPI-MS) is examined here for the detection of four tricyclic antidepressants: imipramine, desipramine, amitriptyline, and clomipramine. About 30 ps laser pulses at either 213 nm (5.8 eV) or 355 nm (3.5 eV) are used for desorption of samples under vacuum, 7.9 eV (157 nm) fluorine laser pulses are used for post-ionization, and the ions so formed are detected by time-of-flight mass spectrometry. Detection of imipramine by 213 nm ps-LDPI-MS shows less fragmentation than either 355 nm ps-LDPI-MS or prior results from 800 nm fs-LDPI-MS. Ionization energies of imipramine, desipramine, amitriptyline, and clomipramine are predicted using density functional theory calculations and used to explain the corresponding ps-LDPI-MS data for these four compounds as resulting from single-photon ionization. The experimental observation of low-mass amine-containing fragments with calculated ionization energies below 7.9 eV is attributed mostly to dissociation during laser desorption, followed by single-photon ionization of the neutral fragments rather than the more traditional mechanism of unimolecular dissociation following single-photon ionization of the parent molecule.