There are a variety of effective pharmacological and other medical treatments for depression; some induce sedation and improve sleep, some increase arousal and interfere with sleep, and others are neutral with respect to sleep. In most cases the effects on sleep are variable, with some individuals experiencing benefits and others experiencing worsening or no effect on their sleep. The American Academy of Sleep Medicine (AASM) has published consensus guidelines for treating insomnia (SchutteRodin, Broch, Buysse, Dorsey, & Sateia, 2008). The algorithm from the AASM (see Figure 2.1) suggests to first evaluate cost, and then preference and availability options for Cognitive Behavior Therapy for Insomnia (CBT-I), pharmacologic, and combined treatments. It is of note that NIH consensus guidelines (National Institutes of Health State, 2005) and British Association of Pharmacotherapy guidelines (Wilson et al., 2010) are that CBT-I should be the frontline treatment, and CBT-I is at the top of the AASM algorithm. Once a decision is made to proceed with pharmacotherapy, the algorithm presents a sequence in which the physician begins with a full dose antidepressant and a Food and Drug Administration (FDA)-approved hypnotic such as benzodiazepine receptor agonist (BzRA) or ramelteon. Following a poor sleep response, the second step in the algorithm is to reconsider the diagnosis and consider switching therapy to CBTI or a combined approach. If there is non-response following this new approach, a different BzRA or ramelteon trial begins. Following a poor response to these approaches, a sedating antidepressant is suggested. Thus, all things considered, the suggestion of a sedating antidepressant is one of the last recommended options because other approaches have better efficacy and safety data available (Riemann et al., 2002; Wilson et al., 2010).