Ketamine for major depressive disorder during an inpatient psychiatric admission: Effectiveness, adverse events, and lessons learned.

OBJECTIVE: Most studies examining the efficacy of ketamine for Major Depressive Disorder (MDD) have been conducted in outpatient or mixed inpatient/outpatient settings. Less is known about effectiveness and tolerability of ketamine for psychiatrically hospitalized patients. Efficacy and tolerability data from a naturalistic sample of acute inpatients may help inform institutions considering ketamine therapy for inpatient services. METHODS: We performed a retrospective chart review of inpatients with non-psychotic MDD treated during the initial 3 years of a ketamine infusion program. Treatment effectiveness was defined using change in Montgomery Asberg Depression Rating Scale (MADRS) scores over five infusions. MDD treatment response was defined by a 50 % reduction of MADRS score, and remission was defined as MADRS score ≤ 10 at any point during the treatment. We also report the frequency of adverse events. RESULTS: 41 patients with MDD were treated and had outcome data. 19 patients (46.5 %) met criteria for response and 15 patients (26.5 %) met criteria for remission during treatment. Four patients (10 %) had adverse psychological or behavioral outcomes. LIMITATIONS: MADRS scales were administered by psychiatrists, psychologists, and trainees in each discipline who did not undergo standardized training in scale administration. Consistent data regarding the race/ethnicity of the patients was not available. CONCLUSION: Twice weekly racemic ketamine infusion is an effective treatment option for patients hospitalized with MDD. Unmonitored or at home ketamine therapy may pose substantial risks.

National Network of Depression Centers' Recommendations on Harmonizing Clinical Documentation of Electroconvulsive Therapy.

ABSTRACT: Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications.

A parallel cholinergic brainstem pathway for enhancing locomotor drive.

The brainstem locomotor system is believed to be organized serially from the mesencephalic locomotor region (MLR) to reticulospinal neurons, which in turn project to locomotor neurons in the spinal cord. We identified brainstem muscarinoceptive neurons in lampreys (Petromyzon marinus) that received parallel inputs from the MLR and projected back to reticulospinal cells to amplify and extend the duration of locomotor output. These cells responded to muscarine with extended periods of excitation, received direct muscarinic excitation from the MLR and projected glutamatergic excitation to reticulospinal neurons. Targeted blockade of muscarine receptors over these neurons profoundly reduced MLR-induced excitation of reticulospinal neurons and markedly slowed MLR-evoked locomotion. The presence of these neurons forces us to rethink the organization of supraspinal locomotor control, to include a sustained feedforward loop that boosts locomotor output.

Initiation of locomotion in lampreys.

The spinal circuitry underlying the generation of basic locomotor synergies has been described in substantial detail in lampreys and the cellular mechanisms have been identified. The initiation of locomotion, on the other hand, relies on supraspinal networks and the cellular mechanisms involved are only beginning to be understood. This review examines some of the findings relative to the neural mechanisms involved in the initiation of locomotion of lampreys. Locomotion can be elicited by sensory stimulation or by internal cues associated with fundamental needs of the animal such as food seeking, exploration, and mating. We have described mechanisms by which escape swimming is elicited in lampreys in response to mechanical skin stimulation. A rather simple neural connectivity is involved, including sensory and relay neurons, as well as the brainstem rhombencephalic reticulospinal cells, which act as command neurons. We have shown that reticulospinal cells have intrinsic membrane properties that allow them to transform a short duration sensory input into a long-lasting excitatory command that activates the spinal locomotor networks. These mechanisms constitute an important feature for the activation of escape swimming. Other sensory inputs can also elicit locomotion in lampreys. For instance, we have recently shown that olfactory signals evoke sustained depolarizations in reticulospinal neurons and chemical activation of the olfactory bulbs with local injections of glutamate induces fictive locomotion. The mechanisms by which internal cues initiate locomotion are less understood. Our research has focused on one particular locomotor center in the brainstem, the mesencephalic locomotor region (MLR). The MLR is believed to channel inputs from many brain regions to generate goal-directed locomotion. It activates reticulospinal cells to elicit locomotor output in a graded fashion contrary to escape locomotor bouts, which are all-or-none. MLR inputs to reticulospinal cells use both glutamatergic and cholinergic transmission; nicotinic receptors on reticulospinal cells are involved. MLR excitatory inputs to reticulospinal cells in the middle (MRRN) are larger than those in the posterior rhombencephalic reticular nucleus (PRRN). Moreover at low stimulation strength, reticulospinal cells in the MRRN are activated first, whereas those in the PRRN require stronger stimulation strengths. The output from the MLR on one side activates reticulospinal neurons on both sides in a highly symmetrical fashion. This could account for the symmetrical bilateral locomotor output evoked during unilateral stimulation of the MLR in all animal species tested to date. Interestingly, muscarinic receptor activation reduces sensory inputs to reticulospinal neurons and, under natural conditions, the activation of MLR cholinergic neurons will likely reduce sensory inflow. Moreover, exposing the brainstem to muscarinic agonists generates sustained recurring depolarizations in reticulospinal neurons through pre-reticular effects. Cells in the caudal half of the rhombencephalon appear to be involved and we propose that the activation of these muscarinoceptive cells could provide additional excitation to reticulospinal cells when the MLR is activated under natural conditions. One important question relates to sources of inputs to the MLR. We found that substance P excites the MLR, whereas GABA inputs tonically maintain the MLR inhibited and removal of this inhibition initiates locomotion. Other locomotor centers exist such as a region in the ventral thalamus projecting directly to reticulospinal cells. This region, referred to as the diencephalic locomotor region, receives inputs from several areas in the forebrain and is likely important for goal-directed locomotion. In summary, this review focuses on the most recent findings relative to initiation of lamprey locomotion in response to sensory and internal cues in lampreys.