Although quality of life (QoL) in patients with ALS has been shown to be independent of physical function and to be maintained over time, the status of psychological health over the disease course has not been studied using an ALS-specific instrument. It is also uncertain how three common interventions – antidepressants, percutaneous endoscopic gastrostomy (PEG), and non-invasive ventilatory support (NIPPV) – influence psychological health. We performed a retrospective review of the Negative Emotion subscale (NES) score, a measure of psychological health within the ALS-Specific QoL Instrument. Analysis of 72 patients over three months, and of a subset of 48 over six months, showed stability of psychological health despite a decline in the ALS Functional Rating Scale-Revised to 88.4% of baseline at three months and 82.6% at six months. NES did not change after antidepressants, PEG, or NIPPV, although there was a suggestion of improvement with antidepressants in a subgroup. In conclusion, as with overall QoL, psychological health of ALS patients as measured with an ALS-specific instrument does not decline as physical function is lost. Supports found in a multidisciplinary ALS clinic may influence expectations, facilitate response shift, and stabilize psychological health while masking the independent effects of specific interventions.