We analytically derive an amplitude equation for the weakly nonlinear evolution of the linearly most amplified response of a non-normal dynamical system. The development generalizes the method proposed in Ducimetière et al. (J. Fluid Mech., vol. 947, 2022, A43), in that the base flow now arbitrarily depends on time, and the operator exponential formalism for the evolution of the perturbation is not used. Applied to the two-dimensional Lamb–Oseen vortex, the amplitude equation successfully predicts the nonlinearities to weaken or reinforce the transient gain in the weakly nonlinear regime. In particular, the minimum amplitude of the linear optimal initial perturbation required for the amplitude equation to lose a solution, interpreted as the flow experiencing a bypass (subcritical) transition, is found to decay as a power law with the Reynolds number. Although with a different exponent, this is recovered in direct numerical simulations, showing a transition towards a tripolar state. The simplicity of the amplitude equation and the link made with the sensitivity formula permits a physical interpretation of nonlinear effects, in light of existing work on Landau damping and on shear instabilities. The amplitude equation also quantifies the respective contributions of the second harmonic and the spatial mean flow distortion in the nonlinear modification of the gain.